my diagnose

ARTERIAL GAS EMBOLISM

2009-01-05T05:33:00.000-08:00

ARTERIAL GAS EMBOLISM - Jacqueline J. Wu, MD; Ruben Peralta, MD, FACS
BASICS
DESCRIPTION
• Arterial gas embolisms are caused by the entry of gas into the pulmonary veins or directly into the arteries of the systemic circulation.
- Gas may enter arteries as a result of overexpansion of lungs by decompression barotraumas.
- May result from paradoxical embolus
• Emboli can travel to any artery, but the most serious consequences occur when they affect the cerebral or coronary circulation.
• Synonym(s): Gas embolism; Air embolism
ALERT
Any diver who has an onset of new symptom(s) or sign(s) after recently completing a Self-Contained Underwater Breathing Apparatus. SCUBA dive of any type, to any depth, for any period of time: Serious consideration must be given that such a patient sustained a dive-related injury.
GENERAL PREVENTION
• Strict adherence to diver safety protocols, especially including the buddy system
• No diving after any dive injury or with any medical condition until evaluated and approved by a physician knowledgeable about diving medicine
EPIDEMIOLOGY
• Predominant age: Young adult
• Predominant sex: Male > Female
Prevalence
Estimated (based on injury/mortality reports collected by Divers Alert Network) to occur in approximately 4 per 100,000 sport divers per year
RISK FACTORS
• Surgery: Recent craniotomy with patient in upright position, cardiothoracic (with cardiopulmonary bypass), hip replacement, Caesarian section
• SCUBA: Arterial gas embolism is the most serious and rapidly fatal of all SCUBA diving injuries and is second only to drowning as the leading cause of death associated with sport diving. Arterial gas embolism occurs on ascent; from alveolar rupture; time to the manifestation of symptoms is nearly always 10 minutes.
• History of patent foramen ovale has been associated with a >4-fold increase in decompression illness events and 2-fold more ischemic brain lesions than in divers without this condition.
ETIOLOGY
• Cerebral air embolism
- Air bubbles occlude the brain vasculature
- ICP increases
- Unequal distribution of blood in the brain causes hyperemia and ischemia.
- Small bubbles irritate vascular wall causing breakdown of blood-brain barrier; small size allows rapid absorption and may cause only brief interruption of cerebral blood flow.
- Larger air bubbles take longer to absorb (up to several hours) and can cause primary ischemic injury with diffuse brain edema and increased ICP.
• Coronary air embolism: Caused by obstruction of coronary arteries by an air bubble
- Temporary ischemia of myocardium
- Labile BP
- Dysrhythmias
- Cardiac failure and/or arrest
• Obstruction is possible in any artery.
- Small emboli in the vessels of skeletal muscles and viscera are well-tolerated.
- Arterial gas embolisms to coronary and cerebral arteries are especially serious or fatal because of the vulnerability of heart and brain to short periods of ischemia.
ASSOCIATED CONDITIONS
• Pulmonary barotrauma leading to arterial gas embolism can also cause pneumomediastinum, subcutaneous emphysema, pneumopericardium, pneumothorax, and pneumoperitoneum.
• Always consider the possibility of decompression sickness in addition to arterial gas embolism in any SCUBA diver who has recently completed a dive.

DIAGNOSIS
SIGNS AND SYMPTOMS
• Cerebral air embolism
- Dizziness
- Chest pain
- Cardiac arrythmia
- Paresthesias
- Minor motor weakness
- Convulsions
- Paralysis
- Nausea
- Visual disturbances
- Gas bubbles in vessels of retina
- Headache
- Asymmetric pupils
- Hemianopia
- Bradypnea
- Cheyne-Stokes breathing
- Aphasia
- Mental status changes ranging from subtle to total lack of consciousness
• Coronary arterial embolism
- Cardiac arrythmias
- Cardiac arrest
ALERT
Anesthesia and/or analgesics alter the symptomatology and may complicate evaluation of the patient's clinical status. Delayed recovery from general anesthesia may be a clue to cerebral arterial embolism.
TESTS
Lab
• Hematocrit: Increased, indicating volume depletion and extravascular shift of fluid into injured tissues
• Serum creatine kinase: Correlation between creatine kinase activity and outcome suggests that elevated serum level of this enzyme may be a marker for size and severity of arterial gas embolism.
• Urinalysis: Increased specific gravity indicates volume depletion.
Imaging
• Chest radiograph to rule out pneumothorax
• ECG
• CT scan: Changes often very subtle
• MRI: Can sometimes show increased volume of water in injured tissue (not very reliable)
DIFFERENTIAL DIAGNOSIS
Decompression sickness
TREATMENT
PRE-HOSPITAL
• General
- Life-saving measures (e.g., CPR) must take precedence to sustain life.
- Endotracheal intubation for somnolent or comatose patient
- Highest possible concentration of oxygen: Eliminates gas in the bubbles by establishing diffusion gradient that favors egress of gas from bubbles
- Place patient in flat, supine position (head down position may aggravate cerebral edema that develops).
• Hyperbaric oxygen
- 1st-line treatment of choice for arterial gas embolism: Immediate transport to a suitable hyperbaric chamber for recompression as soon as possible; do not delay because of nonessential procedures
- 100% oxygen at pressure above that of the atmosphere at sea level
- Decreases bubble size
- Prevents cerebral edema
- For assistance and advice in locating the nearest treatment chamber in your area (worldwide), call Divers Alert Network (DAN) at any hour (919) 684-4326.
• IV fluids
- To counteract hemoconcentration seen in gas embolism
- Colloids preferred over crystalloid (latter may promote cerebral edema)
- Goal is normovolemia
STABILIZATION
• See"Treatment" and "General Measures."
• Hospital-based hyperbaric chamber capable of performing a U.S. Navy Table 6A recompression (165 feet of seawater)
GENERAL MEASURES
• CPR
• Keep patient recumbent while maintaining patent airway.
• Maintain hydration with IV fluids.
• Frequent neurologic checks in the acute pretreatment and treatment phases
Diet
Nothing to be consumed until after treatment
Activity
None until after treatment
SPECIAL THERAPY
IV Fluids
• Colloids preferred over crystalloid
• Achieve normovolemia
MEDICATION (DRUGS)
First Line
Oxygen
• As high a concentration as possible
• Transfer to facility with hyperbaric chamber as soon as possible
Second Line
• Heparin
- Prevents platelet clumping
- Studies of its use are inconsistent.
• Barbituates (if indicated)
- For suppression of seizures
- Reduce ICP
- Decrease cerebral oxygen consumption
• Lidocaine
- Decreases ICP
- Improves recovery of somatosensory evoked potential following cerebral air embolism
- Preserves cerebral blood flow
FOLLOW-UP
PROGNOSIS
Complete to partial resolution with adequate treatment
COMPLICATIONS
• Long-term serious neurologic impairments
• Death
PATIENT MONITORING
Complete neurologic assessment at 1, 3, 6, and 12 months
REFERENCES
1. Muth CM, Shank ES. Gas embolism. N Engl J Med. 2000; 342:476-482.
2. Vann RD, Dovenbarger JA. Reports on decompression illness. Diving fatalities and project dive exploration, the Divers Alert Network Annual Review of Recreational Scuba Driving Injuries and Fatalities. 2002 Data Durham: Divers Alert Network. 2004:1-152.
3. Van Hulst RA, Klein J, Lachmann B. Gas embolism: Pathophysiology and treatment. Clin Physiol Funct Imaging. 2003;23:237-246.
4. Davis J. Medical Examination of Sport Scuba Divers, 2nd ed. San Antonio, TX: Medical Seminars; 1986.

ARTERIAL EMBOLUS AND THROMBOSIS

2009-01-05T02:05:00.000-08:00

ARTERIAL EMBOLUS AND THROMBOSIS - Jeremy Golding, MD
BASICS
DESCRIPTION
• Acute loss of perfusion distal to occlusion of major artery owing to
- Embolus that migrates to point of occlusion or
- Clot intrinsic to point of occlusion (thrombosis)
• Both are true emergencies.
• Following obstruction of artery, soft coagulum forms both proximally and distally in areas of stagnant flow.
• As clot extends, collateral pathways become involved, and process becomes self-propagating.
• Ultimately, venous circulation can become involved.
• Extent of vascular compromise is critical and determines "golden" period of 4-6 hours. After this time, the profound ischemia leads to irreversible cellular death.
• Distribution of emboli
- Femoral artery: 30%
- Iliac artery: 15%
- Aortic bifurcation: 10%
- Popliteal artery: 10%
- Brachial: 10%
- Mesenteric arteries: 5%
- Renal: 5%
- Cerebral (estimated): 15-20%
• System(s) Affected: Cardiovascular; Hematologic/lymphatic/immunologic
GENERAL PREVENTION
• Anticoagulation in atrial arrhythmia
• Reduction of atherosclerosis risk factors
EPIDEMIOLOGY
• 50-100/100,000 hospital admissions
• A leading cause of limb loss in elderly
• Predominant age: Elderly
• Predominant sex: Male > Female
• Rare in children and during pregnancy
RISK FACTORS
Drug abuse
Genetics
Can be associated with inheritable hypercoagulable and premature atherosclerotic syndromes
ETIOLOGY
• Emboli
• Cardiac
- Atrial flutter/fibrillation
- Valve disease
- Myocardial infarction
- Cardiomyopathy
- Cardiac tumors
- Endocarditis
• Aneurysms: Cardiac, aortic, peripheral
• Thrombosis
- Atherosclerotic occlusive disease
- Aortic and peripheral aneurysms, especially popliteal
- Hypercoagulable states
- Venous gangrene
- Drug abuse
- Heparin allergy (heparin-induced thrombocytopenia)
- Vascular bypass
• Trauma
- Blunt
- Penetrating
- Vascular and cardiac interventional procedures
• Venous thrombosis with patent foramen ovale (paradoxical embolus)
ASSOCIATED CONDITIONS
• Acute mesenteric ischemia
• Renal infarction
• Carotid/cerebrovascular accident
• Multiple emboli
• Digital microembolization

DIAGNOSIS
SIGNS AND SYMPTOMS
• To estimate occlusion location
- Symptoms typically start 1 joint below occlusion.
- Palpable pulses absent below occlusion and accentuated above.
• The 5 Ps: If any one is present, frequent re-evaluations indicated. Proximal occlusions lead to more rapid progression of findings. Occlusion at aortic bifurcation can produce bilateral findings.
- Pain: Diffuse in distal area. If persists, crescendo in nature. Predominates as 1st symptom in embolism. Not alleviated by change of position.
- Pulselessness: Mandatory for diagnosis of embolism or thrombosis. Pedal pulses subject to observer error. Always compare to opposite limb.
- Pallor: Skin color pale early, cyanotic later. Check extremity temperature left to right and top to bottom. Look for signs of chronic ischemia: skin atrophy, loss of hair, thick nails.
- Paresthesia: Numbness early with thrombosis. Light touch 1st to be lost. Not reliable in diabetics. Loss of pain and pressure indicate advanced ischemia.
- Paralysis: Motor defect occurs after sensory and indicates profound ischemia.
TESTS
• EKG
• Special tests
• Noninvasive/indirect
- Doppler: Presence or absence of flow
- Ankle/arm index (AAI; aka ankle/brachial index [ABI]) = dorsal pedal/posterior tibial pressure divided by brachial pressure;
- AAI >0.30 favorable (normal >1)
Lab
For preoperative evaluation, elucidation of cause, or documentation of ischemia severity
• Myocardial/muscle isoenzymes
• Coagulation parameters
• Blood pH/bicarbonate
• Urine myoglobin
• Electrolytes
Imaging
Noninvasive/direct: Duplex imaging if time permits
Diagnostic Procedures/Surgery
Arteriography
• Rarely indicated preoperatively in threatened limb
• May help differentiate thrombosis from embolus in nonthreatened limb
• Useful with occluded grafts
DIFFERENTIAL DIAGNOSIS
• Emboli vs. thrombosis
• Emboli
- Myocardial diseases: Myocardial infarction, arrhythmias (e.g., atrial fibrillation), aneurysms
- Pain as 1st symptom
• Thrombosis
- Absence of heart disease: Infarction, arrhythmias
- Chronic vascular history
- Bilateral changes of chronic ischemia
- Numbness rather than pain as 1st symptom
- Vascular procedures: Bypass/interventional
• Other conditions
- Acute aortic dissection (chest or back pain)
- Acute deep vein thrombosis (massive swelling and warm skin)
- Low flow states
TREATMENT
GENERAL MEASURES
• Time is of the essence.
- Unless contraindicated, systemic heparinization to decrease clot propagation and prophylaxis against further emboli
- Resuscitation and stabilization of patient to extent permitted by time
- Triage, based on detailed exam, history, and Doppler examination, determines appropriate therapy.
• Early subcritical stenosis criteria
- Mild ischemic pain
- Normal neurologic exam
- Capillary refill present
- Arterial signals present by Doppler in distal extremity
- Ankle/arm index >0.30
- Treatment
 Heparin (see "Medications")
 Arteriography
- Embolism
 Surgical removal if acceptable operative risk, for example, balloon embolectomy
 Anticoagulation versus intra-arterial thrombolytics if prohibitive risk
- Thrombosis
 Trial of thrombolytics and correction of arterial defect if good risk
 Anticoagulation if poor risk or thrombolytics contraindicated
• Critical stenosis criteria
- Ischemic pain
- Mild neurologic deficit
- Weakness of dorsiflexion
- Minimal sensory loss: Light touch and/or vibratory
- No pulsatile flow by Doppler
- Venous flow present
- Treatment
 Time to intervention is critical
 Heparin (see "Medications")
 Arteriography
 Individualize thrombolysis and/or operative procedure (depending on extent of thrombosis and amenability for surgical removal)
 Thrombolysis to optimize alternatives
 Adjunctive operative therapy
 Intraoperative lytic therapy: Bypass, patch angioplasty
• Late (nonsalvageable) criteria
- Profound sensory loss
- Muscle paralysis
- Absent capillary refill
- Skin marbling
- Muscle rigor
- No arterial or venous signals by Doppler
- Treatment
 Arteriography usually not warranted
 Attempts at reperfusion contraindicated
 Anticoagulation
 Definitive amputation, if possible
MEDICATION (DRUGS)
First Line
• Heparin
- 80-100 U/kg IV loading dose (~5,000-10,000 U)
- Continuous infusion sufficient to double PTT, generally 18 U/kg/h
• Contraindications
- Heparin:
 Allergy
 Bleeding diathesis
 Trauma (e.g., head injury)
 Hematuria/hemoptysis
 Acute aortic dissection
- tPA/Urokinase
 Nonsalvageable ischemia
 Recent MI
 Aneurysm
 Aortic dissection
 Trauma
 Uncontrolled hypertension
 Recent operative procedure
Second Line
Multiple thrombolytics in development
SURGERY
Angioplasty, Thromboembolectomy
FOLLOW-UP
PROGNOSIS
• 90% good outcome with prompt treatment
• Delayed/untreated associated with high mortality and limb loss
• 20-30% hospital mortality associated with causative factors
COMPLICATIONS
• Acidosis
• Myoglobinuria and acute renal failure
• Hyperkalemia
• Recurrent occlusion
• Failure to remove clot/obstruction
• Compartment syndromes/reperfusion syndrome, delayed or acute: Predisposing factors include
- Combined arterial injury
- Profound and prolonged ischemia
- Hypotension
• Clinical findings of compartment syndrome
- Severe pain
- Pain with passive muscle movement
- Hypesthesias of nerves in compartment
- Paralysis of nerves, especially peroneal foot drop
- Tender, tense edema
- Compartment pressure >30-45 mm Hg
• Consequences of unrecognized compartment syndrome
- Acute
 Amputation
 Sepsis
 Myoglobin renal failure
 Shock
 Multiple organ failure
- Delayed
 Ischemic contracture
 Infection
 Causalgia
 Gangrene
• Treatment of compartment syndrome is fasciotomy.
PATIENT MONITORING
Postoperative monitoring
• Anticoagulation
• Establish brisk diuresis.
• Continued resuscitation and diagnosis, including echocardiography and other studies (see "Causes" and "Risk Factors")
• Monitor perfusion stability.
• Treat/eliminate causative factors.
REFERENCES
1. Antithrombotic therapy in peripheral arterial occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest.2004 Sep;126(3 Suppl):609S-26S. Available at www.ngc.gov.
2. Townsend. Sabiston Textbook of Surgery, 17th ed. Boston: Saunders, 2004.
3. Brewster DC, Chin AK, Fogarty TJ. Arterial thrombosis. In: Rutherford RB, ed. Vascular Surgery, 3rd ed. Philadelphia: WB Saunders; 1989.
4. Miller DC, Roon AJ, eds. Diagnosis and Management of Peripheral Vascular Diseases. Menlo Park, CA: Addison-Wesley; 1982.
5. Rutherford RB, Flannigan DP, Gupta SK, et al. Suggested standards of reports dealing with lower extremity ischemia. J Vasc Surg. 1986;64:80-94.

APPENDICITIS, ACUTE

2009-01-05T02:03:00.000-08:00

APPENDICITIS, ACUTE - Andrew H.Fenton, MD
BASICS
DESCRIPTION
Acute inflammation of the vermiform appendix
• 1st described by Fitz in 1886
• McBurney described point of maximal tenderness
EPIDEMIOLOGY
• Predominant age
- Ages 10-30: Male > Female (3:2)
- Over age 30: Male = Female
- Rare in infancy
• Predominant sex: Slight male predominance
Incidence
Lifetime incidence 1 in every 15 persons (7%)
Prevalence
• 10/100,000
• Most common acute surgical condition of abdomen
ALERT
Pregnancy Considerations
• Most common extrauterine surgical emergency
• 1 in 2,000 pregnancies
• Difficult diagnosis
• Appendix displaced superolaterally by gravid uterus
• Fetal mortality rate: 2-8.5%
RISK FACTORS
• Adolescent males
• Familial tendency
• Intra-abdominal tumors
Genetics
Unknown
PATHOPHYSIOLOGY
Obstruction of appendiceal lumen
• Fecaliths (most common)
• Lymphoid tissue hypertrophy
• Inspissated barium
• Vegetable, fruit seeds and other foreign bodies
• Intestinal worms (ascarids)
• Strictures

DIAGNOSIS
SIGNS AND SYMPTOMS
• Abdominal pain (100%): Periumbilical, then right lower quadrant; lessened with flexion of thigh
• Muscle guarding
• Anorexia (almost 100%)
• Nausea (90%)
• Vomiting (75%); mild
• Obstipation
• Diarrhea; mild
• Sequence of symptom appearance (95%): Anorexia, then abdominal pain, then vomiting
• Slight temperature elevation (1C)
• Slight tachycardia
• Patient frequently lies motionless with right thigh drawn up
• Maximal tenderness at McBurney point
• Direct and referred right-lower-quadrant tenderness
• Voluntary and involuntary guarding
• Cutaneous hyperesthesia at T10-12
• Rovsing sign: Right-lower-quadrant pain with palpatory pressure in left lower quadrant
• Psoas sign: Pain with right thigh extension
• Obturator sign: Pain with internal rotation of flexed right thigh
• Retrocecal appendix: Flank tenderness in right lower quadrant
• Pelvic appendix: Local and suprapubic pain on rectal exam
ALERT
Pediatric Considerations
• Decreased diagnostic accuracy
• Higher fever, more vomiting
Geriatric Considerations
Decreased diagnostic accuracy
History
Cornerstone of diagnosis, with clinical findings
Physical Exam
• Diagnostic laparoscopy: Consider in young adult females
• Rectal and pelvic examinations
• May need intensive in-hospital observation to allow serial examination
TESTS
Lab
• Moderate leukocytosis: 10,000-18,000/mm3 in 75%
• Moderate polymorphonuclear predominance
• hCG to rule out ectopic pregnancy
• Urinalysis
- Elevated specific gravity
- Hematuria (sometimes)
- Pyuria (sometimes)
- Albuminuria (sometimes)
• Drugs that may alter lab results
- Antibiotics
- Steroids
Imaging
• Used in differential diagnosis and to detect complications
• CT scan: Diagnostic test of choice; also for abscess (1)[B]
Diagnostic Procedures/Surgery
Diagnostic laparoscopy, especially in fertile women (1)[A]
Pathological Findings
• Acute appendix inflammation
• Local vascular congestion
• Obstruction
• Gangrene
• Perforation with abscess (15-30%)
DIFFERENTIAL DIAGNOSIS
• Any cause of acute abdomen
• 75% of erroneous diagnoses accounted for by
- Acute mesenteric lymphadenitis
- No organic pathologic condition
- Acute pelvic inflammatory disease
- Ovarian cyst torsion
- Ruptured graafian follicle
- Acute gastroenteritis
• Also consider
- Urologic causes
- Testicular torsion
- Inflammatory bowel disease
- Colonic disorders
- Other gynecologic diseases
TREATMENT
GENERAL MEASURES
• For nonsurgical patients, antibiotic coverage (e.g., quinolone and metronidazole)
• Recurrence rate too high in other patients to recommend antibiotics as a primary therapy
Diet
NPO
Nursing
Pre-op preparation
SPECIAL THERAPY
IV Fluids
• Fluid resuscitation with LR
• Correct fluid and electrolyte deficits.
MEDICATION (DRUGS)
First Line
• Uncomplicated acute appendicitis: 1 preoperative dose of broad-spectrum antibiotic (2)[A]
- Cefoxitin (Mefoxin)
- Cefotetan (Cefotan)
• Gangrenous or perforating appendicitis
- Broadened antibiotic coverage for aerobic and anaerobic enteric pathogens
- Adjust dosage and choice of antibiotic based on intraoperative cultures.
- Continue antibiotics for 7 days postoperatively or until patient becomes afebrile with normal white count.
- Pathogens usually sensitive to ampicillin, gentamicin, and clindamycin
• Contraindications: Documented allergy to specific antibiotic
• Precautions: Adjust antibiotic dosages for elderly and patients with renal failure.
• Significant possible interactions: Refer to manufacturer's literature for each drug.
Second Line
• Metronidazole (Flagyl): Anaerobic coverage only
• Ampicillin-sulbactam (Unasyn)
• Ticarcillin-clavulanate (Timentin)
• Piperacillin-tazobactam (Zosyn)
SURGERY
Inpatient surgery is appropriate measure
• Immediate appendectomy; laparoscopic favored unless perforation (3)[A]
• Drainage of abscess, if present
FOLLOW-UP
DISPOSITION
Admission Criteria
Complicated appendicitis
Discharge Criteria
Tolerating PO; return of bowel function; afebrile; normal WBC
Issues for Referral
Follow-up with surgeon 1-2 weeks
PROGNOSIS
• Generally uncomplicated course in young adults with nonruptured appendicitis
• Factors increasing morbidity and mortality
- Extremes of age
- Appendiceal rupture
• Morbidity rates
- Nonperforated appendicitis: 3%
- Perforated appendicitis: 47%
• Mortality rates
- Unruptured appendicitis: 0.1%
- Ruptured appendicitis: 3%
- Patients >60 years of age: 50% of deaths from appendicitis
- Elderly patient with ruptured appendix: 15%
ALERT
Pediatric Considerations
• Rupture earlier
• Rupture rate: 15-50%
Geriatric Considerations
Rupture rate: 67-90%
COMPLICATIONS
• Wound infection
• Intra-abdominal abscess; lower rate with antibiotic prohylaxis [2A]
• Fecal fistula
• Intestinal obstruction
• Incisional hernia
• Liver abscess (rare)
• Paralytic ileus
PATIENT MONITORING
Routine visits at 2 and 6 weeks after surgery
REFERENCES
1. Mun S, Ernst RD, Chen K, et al. Rapid CT diagnosis of acute appendicitis with IV contrast material. Emerg Radiol. 2005;17:1-4 [e-pub ahead of print]
2. Andersen BR, Kallehaue FL, Andersen HK. Antibiotics versus placebo for prevention of postoperative infection after appendectomy. The Cochrane Database of Systematic Reviews 2006 issue 1. John Wiley  Sons, Ltd.
3. Sauerland S, Lefering R, Neugebauer EAM. Laparoscopic versus open surgery for suspected appendicitis. The Cochrane Database of Systematic Reviews 2006 issue 1. John Wiley  Sons, Ltd

AORTIC VALVULAR STENOSIS

2009-01-05T02:01:00.000-08:00

AORTIC VALVULAR STENOSIS - Suzanne Klainer, MD
BASICS
DESCRIPTION
Acquired or congenital obstruction to left-ventricular outflow across aortic valve caused by decreased valve area. Is classified as mild, moderate, or severe based on measured area.
GENERAL PREVENTION
Prevention of Rheumatic Heart Disease for acquired postinflammatory aortic stenosis.
EPIDEMIOLOGY
• Predominant age (1)
- 30 years: Congenital
- 30-70 years: Congenital or rheumatic
- >70 years: Degenerative calcification of aortic valve
• Predominant sex: Male > Female, 2:1
Prevalence (2)
• 1.3% of 65-74 years
• 2.4% of 75-84 years
• 4% of >84 years
• Bicuspid aortic valve: 0.8% of population (3)
ALERT
Geriatric Considerations
Increased incidence of degenerative calcific aortic stenosis
RISK FACTORS
• Unicommissural valve
• Bicuspid valve
• Prior rheumatic fever
• Advanced age
• Hypercholesterolemia
• Metabolic disease (SLE, Fabry)
PATHOPHYSIOLOGY
Resistance to outflow at the aortic orifice causes increased afterload. The left ventricle responds to this pressure overload with thickening of myocardial wall, resulting in left ventricular (LV) dysfunction and CHF as well as increased myocardial oxygen demand.
ETIOLOGY
• Congenital
- Unicuspid valve
- Bicuspid valve: Not inherently stenotic, but becomes so as a result of wear-and-tear thickening and calcification; calcified bicuspid valve is most common cause of isolated aortic stenosis in adults.
- Tricuspid valve with fusion of commissures
- Hypoplastic annulus
• Acquired
- Rheumatic fever (or, rarely, other inflammatory disease)
- Degenerative calcific aortic stenosis in elderly
ASSOCIATED CONDITIONS
• Coronary artery disease (present in 50% of patients)
• Aortic regurgitation (particularly in calcified bicuspid valves and rheumatic disease)
• Mitral valve disease (primarily in rheumatic heart disease)
• LV dysfunction and CHF
• A-fibrillation associated with CHF

DIAGNOSIS
SIGNS AND SYMPTOMS
• Angina pectoris: Most frequent symptom
• Near syncope
• Syncope: Often exertional
• Exertional dyspnea
• Orthopnea
• Paroxysmal nocturnal dyspnea
• Palpitations
• Fatigue
• Neurologic events (transient ischemic attack or cerebrovascular accident) owing to embolization
• Systolic crescendo-decrescendo murmur: Usually best heard at 2nd right sternal border (may have associated thrill); may radiate into carotid arteries
• Ejection (early systolic) click
• Prolonged ejection time
• Delayed, small carotid upstroke
• Delayed/decreased intensity of A2
• Paradoxical splitting of S2
• LV heave
• High-pitched diastolic blow: May be present at left sternal border (associated aortic regurgitation)
History
Above symptoms in elderly patient or one with history congenital heart defect or rheumatic fever
Physical Exam
• Cardiac
- Systolic crescendo-decrescendo murmur RSB, radiating to carotids
- Delayed carotid upstroke
- Left ventricular heave
- Increased intensity of A2
TESTS
ECG
• Conduction defects
• Left-atrial enlargement
• Ventricular arrhythmias
• LV hypertrophy
• ST segment depression
Lab
Elevated BNP
Imaging
• Chest radiograph
- May be normal in compensated, isolated valvular aortic stenosis
- Cardiac hypertrophy early, later cardiomegaly
- Poststenotic dilatation of ascending aorta
- Calcification of aortic valve cusps (may require fluoroscopy to visualize)
• Echocardiography
- Aortic valve morphology, thickening, calcifications
- Decreased aortic valve excursion
- Planimetry of aortic valve area
- LV hypertrophy
- LV ejection fraction
- Chamber dimensions
- Presence or absence of wall-motion abnormalities suggesting coronary artery disease
• Doppler echocardiography
- Transvalvular gradient
- Valve area
- Diastolic function
- Associated aortic regurgitation
Diagnostic Procedures/Surgery
Cardiac catheterization: Recommended for patients undergoing AV replacement at risk for CAD and for assessment of severity when AVR is planned or noninvasive studies are inconclusive (A)
• Identifies transvalvular gradient, valve area, LV ejection fraction, concomitant CAD
Pathological Findings
• LV hypertrophy
• Myocardial interstitial fibrosis
• Aortic valvular calcification in older patients
• 50% incidence of concomitant CAD
DIFFERENTIAL DIAGNOSIS
• Mitral regurgitation
- Either primary or secondary to underlying coronary artery disease or dilated cardiomyopathy
- Usually an apical, high-frequency, pansystolic murmur, often radiating to axilla
• Hypertrophic obstructive cardiomyopathy
- Also systolic crescendo-decrescendo murmur, but best heard at left sternal border and may radiate into axilla
- However, characteristically intensified by changing from squatting to standing and/or by Valsalva maneuver, lessened by changing from standing to squatting
• Aortic supravalvular stenosis
• Discrete subaortic stenosis
TREATMENT
STABILIZATION
Outpatient care except for surgical intervention or comorbid condition requiring hospital care
GENERAL MEASURES
• Asymptomatic patient with noncritical aortic stenosis: Because aortic stenosis is progressive, follow closely with appropriate evaluation.
• All patients should receive endocarditis prophylaxis prior to dental work or invasive procedures regardless of age, cause, or severity of stenosis. (4)[C]
• Patients with stenosis of rheumatic cause should receive (in addition to endocarditis prophylaxis prior to dental work or invasive procedures) rheumatic fever prophylaxis, especially if 35 years or in close contact with young children.
• Screen for and treat comorbid diseases.
- Commonly HTN, CAD, CHF, and A-fib.
ALERT
Pregnancy Considerations
• Severe critical aortic stenosis responds poorly to hemodynamic changes in pregnancy, labor, and delivery.
• Pregnancy should be avoided with critical aortic stenosis; may need Cesarean section for delivery of baby.
Diet
Only restriction is low-sodium diet in presence of CHF
Activity
In known or suspected severe aortic stenosis, vigorous physical activity contraindicated
MEDICATION (DRUGS)
• ACE I is beneficial for treatment of LV dysfunction and associated heart failure, but can cause hypotension in patients with baseline low blood pressure (5) [B].
• Statins: Anecdotal evidence suggest that statins slow progression of AS, however, recent RCT failed to support this claim (6).
• Prophylactic antibiotics for
- Bacterial endocarditis
- Rheumatic fever, where indicated
- See "General Measures"
ALERT
Use antihypertensives cautiously, because they potentially can cause hypotension in AS.
SURGERY
• Aortic valve replacement indicated in
- Patients with symptomatic severe AS, patients with severe AS undergoing CABG, or patients with severe AS undergoing aortic or other valve surgery (4)[A].
- Moderate AS undergoing cardiac surgery (4)[B]
- Asymptomatic patients with critical AS (aortic valve area 0.6.0 cm2), LV dysfunction, abnormal response to exercise, ventricular tachycardia, or increasing cardiomegaly (15 mm) (4)[C]
• Surgical valve replacement consists of removal of stenotic, native valve and placement of prosthetic mechanical or tissue valve.
• Balloon angioplasty of stenotic aortic valves
- May benefit pediatric patient with congenital disease (4)[A]
- In elderly as a bridge to AV replacement, for palliation in patients with serious comorbid conditions, and in patients who require urgent noncardiac surgery (4)[B]
FOLLOW-UP
DISPOSITION
Admission Criteria
See criteria for comorbid conditions.
Discharge Criteria
See criteria for comorbid diseases.
PROGNOSIS
• Mortality following onset of symptoms (7)
- 26% at 1 year
- 57% at 3 years
• Risk of sudden death is 0.4% per year (4)
COMPLICATIONS
• Progressive stenosis
• Sudden death
• Congestive heart failure
• Angina
• Syncope
• Hemolytic anemia
• Bleeding disorder (acquired vWF d/o) (8)
• Infective endocarditis
PATIENT MONITORING
• Symptomatic patients should be examined frequently.
• ECG every 2-5 years to assess progression in the asymptomatic patient with mild/moderate disease, respectively (4)[C]
• Advise patient to immediately report any symptoms referable to AS.
REFERENCES
1. Subramanian E. Surgical pathology of pure aortic stenosis. A study 374 cases. Mayo Clin Proc. 1984;59:683.
2. Stewart et al. Clinical factors associated with calcific aortic valve disease. J Am Coll Cardiol. 1997;29:630.
3. Otto CM, Burwash, Legget, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic and exercise predictors of outcome. Circulation. 1997;95:2262.
4. Bono et al. ACC/AHA task force report. J Am Coll Cardiol 1998;32:1486.
5. Chockalingam et al. SCOPE-AS. Am Heart J. 2004;147(4):E19.
6. Crowell et al. SALTIRE. N Engl J Med. 2005;352:2389-2397.
7. Chizner et al. The natural history of aortic stenosis in adults. Am Heart J 1980;99(4):419-424.
8. Vincentelli, et al. Acquired von Willebrand in aortic stenosis. N Engl J Med. 2003;349:343.
9. Nistri, et al. Frequency of bicuspid aortic valves in young male conscripts by echocardiogram. Am J Cardiol. 2005;96:718.
MISCELLANEOUS
LV is relatively noncompliant in aortic stenosis, thus
• Atrial contraction is important component of diastolic filling.
• Loss of atrial contraction with onset of atrial fibrillation can cause acute clinical and hemodynamic deterioration.

AORTIC DISSECTION

2009-01-04T01:00:00.000-08:00

AORTIC DISSECTION - Jeremy Golding, MD
BASICS
DESCRIPTION
• Intimal tear in aorta resulting in hematoma formation. Accumulating blood in false lumen of arterial wall leads to propagation of this dissection.
• DeBakey classification: Based on origin site
- Type I: Originates in ascending aorta, propagates at least as far as aortic arch
- Type II: Involves only ascending aorta
- Type III: Originates in descending aorta, may propagates proximately or distally
• Stanford classification: More widely used
- Type A: Involves ascending aorta and aortic arch regardless of site of intimal tear
- Type B: Involves descending aorta
• New classification, subdivisions of DeBakey or Stanford
- 1. Classic
- 2. Medial disruption with hematoma formation
- 3. Discrete without hematoma
- 4. Plaque rupture, ulceration
- 5. Iatrogenic
• Synonym(s): Dissecting aneurysm
GENERAL PREVENTION
• Long-term control of hypertension
• Surveillance of aortic root and replacement when appropriate in patients with collagen disorders (e.g., Marfan, Ehlers-Danlos)
EPIDEMIOLOGY
• Predominant age: Depends on cause; commonly present in patients with Marfan syndrome in 3rd and 4th decades; otherwise most common between 6th and 8th decades
• Predominant sex: Male > Female (3:1)
• Mean age: Men 60 years, women 67 years
Incidence
2000 new cases diagnosed annually
Prevalence
US
• Diagnosed in 1 in 10,000 patients admitted to hospital
• Found in 1 in 350 patients at autopsy
RISK FACTORS
• Hypertension in 70% of patients
• Cystic medial necrosis
• Collagen abnormalities
- Marfan syndrome
- Ehlers-Danlos syndrome
• Inflammatory aortitis
• Takayasu arteritis
• Giant cell arteritis
• Congenital abnormalities
- Bicuspid aortic valve
- coarctation
• Pregnancy
• Chest trauma
• Cocaine use
• Cardiovascular surgery
• Elderly
• MDMA (ecstasy) use
• 1-Antitrypsin deficiency
• Smoking
Genetics
Increased incidence among family members
ETIOLOGY
• Cystic medial necrosis
• Iatrogenic during arterial catheterization
ASSOCIATED CONDITIONS
• Ehlers-Danlos syndrome
• Marfan syndrome
• Aortic stenosis
• Coarctation of aorta
• Bicuspid valve
• Turner syndrome
• Osteogenesis imperfecta
• Syphilis
• Relapsing polychondritis
• During pregnancy: Possibly cystic medionecrosis of pregnancy; unclear whether pregnancy is originating factor or contributes to worsening of a pre-existing condition

DIAGNOSIS
SIGNS AND SYMPTOMS
• Abrupt onset of sharp or tearing pain
• Shearing anterior chest pain radiating to interscapular region
• Back pain
• Syncope
• Symptoms of CHF
• Stroke
• Limb ischemia
• Abdominal pain
• Acute myocardial infarction/angina
• Spinal cord syndromes/deficits
• Hypotension or hypertension
• Wide pulse pressure
• Murmur of aortic insufficiency
• Features of tamponade
• Dullness in left lung base (effusion)
• Pulse deficits or asymmetry
• Fever
• 96% of acute aortic dissections can be identified by abrupt onset of sharp thoracic or abdominal pain in the presence of mediastinal widening on chest radiograph and asymmetry of pulses
History
Typical patient is a hypertensive man in his 60s with abrupt onset of severe chest pain.
TESTS
• Electrocardiogram
- Left ventricular hypertrophy
- Nonspecific ST-T changes
- Electrical alternans (in cardiac tamponade)
• Echocardiogram
- Dilated aortic root
- Increased aortic posterior or anterior wall thickness
- Pericardial effusion
- Oscillating intimal flap
Imaging
Chest radiograph, in stable patients
• Widening of superior mediastinum
• Left pleural effusion
• Haziness or enlargement of aortic knob
• Double density of descending aorta
• Irregular aortic contour: >5 mm separation of intimal calcification from outer aortic contour
• Rightward displacement of trachea
• Cardiomegaly
Diagnostic Procedures/Surgery
• (Sensitivity/specificity is indicated for each.)
• Chest CT (88/100%)
- Demonstration of 2 lumens with hematoma formation
- Detection of intimal flap
- Differential flow between 2 lumens
- Compression of true lumen by false lumen
• Spiral CT aortography; more sensitive and specific (99/99%)
• Aortogram (88/94%)
- Demonstration of 2 lumens
- Detection of intimal flap
- Compression of true lumen
- Ulcer-like projections of contrast
- Altered flow patterns
• Transesophageal echocardiography (99/98%): Test of choice for unstable patients
• MRI: If available and patient hemodynamically stable, test of choice for delineation of vascular anatomy (>99/99%)
• Intravascular ultrasonography: May detect with negative transesophageal echocardiography
Pathological Findings
• ~60% of intimal tears occur in proximal ascending aorta. Remainder are between origin of left subclavian artery and ligamentum arteriosum, descending aorta (20%), aortic arch (10%), and abdominal aorta.
• Although medionecrosis is found in normal aging aortas, it is more extensive in patients who develop aortic dissection.
• Cystic medial necrosis is seen in patients with defects in elastin and connective tissue organization (e.g., Marfan, Ehlers-Danlos).
• Death usually is due to rupture and tamponade.
DIFFERENTIAL DIAGNOSIS
• Myocardial infarction
• Pulmonary embolism
• Pneumonia
• Pleurisy
• Pericarditis
• Pneumothorax
• Angina
• Acute pancreatitis
• Penetrating duodenal ulcer
TREATMENT
GENERAL MEASURES
• Admit to ICU for assessment of hemodynamic stability, pain control, BP control
• Intubate; hemodynamically unstable patients
• Medical therapy
- Treatment of choice for descending dissections without complications (Type III)
- Based on decreasing BP and shearing forces of myocardial contractility (dp/dt) to decrease intimal tear and hematoma propagation
- Survival is 60-80% at 4-5 years
• Arterial BP monitoring is critical.
• Careful observation for changes in mentation, neurologic signs, or evidence of organ dysfunction
• Foley catheter to follow urine output
• Swan-Ganz catheterization may be helpful in monitoring cardiac performance and filling pressures during use of vasoactive and cardiodepressive drugs.
• Pain control difficult despite use of narcotics.
Diet
NPO until surgical evaluation is complete and patient classified as medical therapy only
Activity
Bed rest
MEDICATION (DRUGS)
First Line
• Propranolol plus nitroprusside; dosing
- Propranolol: 0.5-1 mg IV q5min until heart rate 60-70 bpm and
- Nitroprusside: Titrated to reduce systolic BP to 100-110 mm Hg (13.3-14.6 kPa)
• Contraindications
- Propranolol
 Bronchial asthma
 Diabetes mellitus
 Raynaud disease
 Sinus bradycardia
 A-V heart block >1st degree
 In presence of MAOIs
 Cardiogenic shock
 Acute CHF
 Right ventricular failure from pulmonary hypertension
- Nitroprusside
 In treatment of compensatory hypertension, that is, arteriovenous shunt
 In patients with inadequate cerebral circulation
 For use during emergency surgery in moribund patients
• Precautions
- Propranolol
 Use cautiously in patients with angina pectoris, cardiac failure, impaired renal or hepatic function, thyrotoxicosis, pre-excitation syndromes, diabetes, or nonallergic bronchospasm.
 Propranolol may produce bradycardia, heart block, or hypotension. Patients should not be suddenly withdrawn from -blockers.
- Nitroprusside
 May not lower BP adequately; another agent may be required.
 In patients with renal or hepatic insufficiency, may cause cyanide toxicity through excessive production of serum thiocyanate. Confusion and hyper-reflexia are early signs of thiocyanate toxicity. Thiocyanate inhibits uptake and binding of iodine; caution with hypothyroidism. Check thiocyanate levels after 48 hours.
 Administration via infusion pump.
 Methemoglobinemia may be seen rarely.
• Significant possible interactions
- Propranolol: Adenosine, albuterol, alfentanil, amiodarone, barbiturates, bromazepam, chlorothiazide, chlorpromazine, chlorpropamide, chlorprothixene, cimetidine, clonidine, dextroamphetamine, diazoxide, dihydroergotamine, diltiazem, disopyramide, tricyclic antidepressants, encainide, epinephrine, flecainide, fluvoxamine, furosemide, glipizide, halofenate, haloperidol, heparin, ibuprofen, indomethacin, insulin, isoniazid, isoproterenol, lidocaine, lidoflazine, methacholine, methyldopa, metoclopramide, naproxen, nifedipine, phenylpropanolamine, procainamide, quinidine, reserpine, rifampin, ritodrine, sulfonylureas, theophylline, thioridazine, tocainide, tubocurarine, verapamil, and warfarin
- Nitroprusside: Clonidine and other antihypertensives may have hypotensive effects.
Second Line
• Labetalol: 10-20 mg IV bolus to a maximum of 300 mg total, then titrated to response with infusion
• Trimethaphan: Infusion rate 1-2 mg/min
• Reserpine: 0.5-2 mg IM q4-8h; onset of action 1-3 hours
• Methyldopa: 250-500 mg q6h; onset of action of 4-6 hours; duration 1-12 hours
SURGERY
• Treatment of choice for all ascending aortic dissections
• Surgical indications for Type III
- Increasing size of hematoma
- Impending rupture
- Inability to control pain
- Bleeding into pleural space
• Endovascular stents, fenestration, and stent grafting
FOLLOW-UP
PROGNOSIS
• Mortality, untreated
- 24 hours: 33%
- 2 weeks: 60%
- 3 months: 90%
• Hospital survival estimate, treated medically and surgically: 70%
• Mortality, ascending dissection treated early surgically: 29-38%
• 10-year survival, treated surgically (all): 40%
• Redissection risk
- 5 years: 13%
- 10 years: 23%
COMPLICATIONS
• Redissection
• Localized saccular aneurysm
• Cardiac tamponade
• Aortic valvular insufficiency
• Progressive aortic enlargement
PATIENT MONITORING
• Maintain systolic BP at 120 mm Hg (16 kPa) or below, as tolerated.
• Routine chest films and/or chest CT may be helpful for patient treated medically long term.
• Follow-up visit at 1 month, then at 3-month intervals. During follow-up, pay careful attention to signs and symptoms of aortic insufficiency, chest or back pain, and development of saccular aneurysms as displayed on chest films.
REFERENCES
1. Beckman JA, O'Gara PT. Diseases of the aorta. Adv Intern Med. 1999;44:267-291.
2. Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection. Eur Heart J. 2001;22:1642.
3. Hartnell GG. Imaging of aortic aneurysms and dissection: CT and MRI. J Thorac Imaging. 2001;16:35-46.
4. Lindsay JJ. Diagnosis and treatment of diseases of the aorta. Curr Probl Cardiol. 1997;22:485-542.
5. Manninen HI, Rasanen H. Intravascular ultrasound in interventional radiology. Eur Radiol. 2000;10:1754-1762.
6. Penco M, Paparoni S, Dagianti A, et al. Usefulness of transesophageal echocardiography in the assessment of aortic dissection. Am J Cardiol. 2000;86(4A):53G-56G.
7. Pretre R, von Segesser LK. Aortic dissection. Lancet. 1997;349:1461-1464.
8. Rogers FB, Osler TM, Shackford SR. Aortic dissection after trauma: Case report and review of literature. J Trauma. 1996;41:906-908.
9. Sommer T, Fehske W, Holzknecht N, et al. Aortic dissection: A comparative study of diagnosis with spiral CT, multiplanar transesophageal echocardiography, and MR imaging. Radiology. 1996;199:347-352.
10. Umana JP, Mitchell RS. Endovascular treatment of aortic dissections and thoracic aortic aneurysms. Semin Vasc Surg. 2000;13:290-298.
11. Vonkodolitsch Y, Schwartz AG, Nienaber CA. Clinical prediction of acute aortic dissection. Arch Intern Med. 2000;160:2977.

ANXIETY

2009-01-03T08:43:00.000-08:00

ANXIETY - Mitzi Wasik, PharmD, BCPS
BASICS
DESCRIPTION (1)
A common acute or chronic, fearful emotion with associated physical symptoms. DSM-IV-R recognizes the following subtypes
• Acute situational anxiety: Response to recent stressful event, usually transient symptoms
• Generalized anxiety disorder (GAD): Persistent underlying anxiety or adjustment disorder with anxious mood and significant symptoms of motor tension, autonomic hyperactivity, and hypervigilance, lasting >6 months
• Panic disorder (PD): Recurrent unexpected attacks with at least one attack (or more) associated with persistent concern about additional attacks, worries about implications of the attack (losing control, having a heart attack), or a significant change in behavior related to the attack; often leads to agoraphobia
• Social phobia (Social Anxiety Disorder): Marked and persistent fear and avoidance of performance or social situations in which the person is exposed to unfamiliar people or scrutiny
• System(s) Affected: Nervous
GENERAL PREVENTION (2)
• Cognitive behavior therapy
• Management of stress, to extent possible
• Relaxation techniques
• Meditation
EPIDEMIOLOGY (3)
Predominant sex: Female > Male (2:1)
Incidence
• 15.7 million Americans suffer from anxiety disorders every year, 30 million will suffer at some point in their lives
• 30% of patients suffering from anxiety seek treatment.
Prevalence
• 12-month prevalence rate
- Panic disorder:1.3-1.7%
- Generalized anxiety disorder
 All ages12.1-12.7%
- Social phobia: 1.7-3.7%
• Onset can occur anytime in life, from adolescent to adulthood
- Women >age 45 are most frequently affected
RISK FACTORS
Social and financial problems, medical illness, family history, lack of social support
Genetics
Panic disorder: Increased concordance in monozygotic versus dizygotic twins
ETIOLOGY
• Panic disorder, social phobia, and obsessive compulsive disorder are associated with genetic factors.
• Mediated by abnormalities of neurotransmitter systems (serotonin, norepinephrine, and gamma-aminobutyric acid [GABA])
ASSOCIATED CONDITIONS
• Depression (commonly)
• Agoraphobia
• Alcohol or substance abuse
• Somatoform disorders

DIAGNOSIS
(1,4)
SIGNS AND SYMPTOMS
History
Symptoms must occur for more days than not for 6 months
Physical Exam
• 3 (or more) criteria are required for diagnosis of GAD. Only one required in children
- Restlessness or feeling keyed up or on edge
- Easily fatigued
- Difficulty concentrating or mind going blank
- Irritability
- Muscle tension
- Sleep disturbances (difficulty falling or staying asleep)
- Difficulty controlling worry
• Persistent worry must cause significant distress, impairment in social, occupational, or other areas of functioning
• Nonspecific signs and symptoms that may be present with different subtypesunrealistic or excessive anxiety or worry, sense of impending doom, nervousness, instability, tachycardia, palpitations, systolic click murmur, hyperventilation, choking sensation, sighing respiration, nausea or abdominal distress, paresthesias, diaphoresis, dizziness or syncope, flushing, muscle tension, tremulousness, restlessness, headache, backaches, and muscle spasm
TESTS
EEG, ECG, etc.
Lab
Laboratory tests are often normal. See Differential Diagnosis for conditions to rule out.
Imaging
Usually none
Diagnostic Procedures/Surgery
Psychologic testing
• Anxiety Disorders Interview Schedule (ADIS), Hamilton's Anxiety Scale (HAM-A), Clinical Global Impression Scale (CGI), DSM-IV-R criteria
DIFFERENTIAL DIAGNOSIS
• Cardiovascular
- Ischemic heart disease, valvular heart disease, cardiomyopathies, myocarditis, arrhythmias, mitral valve prolapse (most symptomatic cases are associated with panic disorder), congestive heart failure, or myocardial infarction
• Respiratory
- Asthma, chronic obstructive pulmonary disease, pulmonary embolism, or pneumonia
• CNS
- Stroke, seizures, dementia, migraine, Parkinson disease, neoplasms
• Metabolic and hormonal
- Hyperthyroidism, pheochromocytoma, adrenal insufficiency, Cushing syndrome, hypokalemia, hypoglycemia, hyperparathyroidism
• Nutritional
- Thiamine, pyridoxine, or folate deficiency, iron deficiency anemia
• Drug-induced anxiety
- Alcohol, sympathomimetics (cocaine, amphetamines, caffeine)
• Withdrawal
- Alcohol, sedative-hypnotics
• Other
- Other psychiatric comorbidities
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient
• Based on careful workup and identification of etiology and subtype of anxiety disorders
• Identify coexistent substance abuse.
• Counseling or psychotherapy along with medications, biofeedback in selected cases
• Serial office visits
Diet
• Limit caffeine intake.
• Avoid alcohol (drug interactions).
Activity
Physical exercise
SPECIAL THERAPY
Complementary and Alternative Medicine
Kava was previously used but is no longer in favor due to liver toxicities.
MEDICATION (DRUGS) (3,5,6,7,8)
First Line
• Conditions
- Acute situational anxiety: Short-term (up to 1 month) treatment with benzodiazepines (2)[B]
- Generalized anxiety disorder
- Escitalopram (Lexapro) 10 mg/day titrated by 10 mg every week to a max of 20 mg/day (10 mg/day max) (1)[A]
- Paroxetine (Paxil) 10 mg daily titrated by 10 mg a week to a max 50 mg/day (20 mg/day most effective dose); (10 mg/day) (1)[A]
- Venlafaxine (Effexor XR) 37.5-75 mg titrated to a max of 225 mg/day (1)[A]
- Imipramine (Tofranil) 50 mg/day (max 200 mg/day, 100 mg in elderly) (1)[A]
- Fluoxetine (Prozac) 10 mg daily up to max of 20-40 mg/day (2)[C]
- Sertraline (Zoloft) 25 mg daily up to max of 200 mg/day (2)[B]
- Buspirone (Buspar) 20-30 mg/day divided b.i.d. to t.i.d. (max 60 mg/day) (1)[A]
• Panic disorder and social phobia: SSRIs, TCAs (e.g., imipramine), buproprion, trazodone, and beta-blockers (2)[B]
Second Line
• Generalized anxiety disorder
- Hydroxyzine 50-100 mg q6h (max 400 mg/day) (1) [A]
• BZDs (short-term use) (1)[A]
- Alprazolam (Xanax) 0.25 mg b.i.d. to t.i.d. increase by 0.25 mg, if needed
- Clonazepam (Klonopin) 0.5 mg t.i.d. to maximum of 1.5-4.5 mg per day
- Diazepam (Valium) 2-5 mg b.i.d. increase by 2 mg if needed
- Lorazepam (Ativan) 0.5 mg b.i.d. to t.i.d. increase by 0.5 mg if needed (response, if any, is slow, often 4-6 weeks)
• Panic disorder
- BZDs may be used short term until TCA or SSRI takes effect (2-3 weeks)
- BZDs may be helpful for initial control of symptoms until the SSRIs or TCAs are effective.
ALERT
Pediatric Considerations
• Reduced dosage of medications in adolescent
• Anxiety often comorbidly exists with ADHD
Geriatric Considerations
• Reduced dosage of medications
• Avoid TCAs and long-acting benzodiazepines.
Pregnancy Considerations
• BZDs: Contraindicated in 1st trimester of pregnancy, and with caution later in pregnancy and during lactation. May cause lethargy and weight loss in nursing infants; avoid breast-feeding if the mother is taking benzodiazepines chronically or in high doses.
• SSRIs: Taper and discontinue, if possible, in 1st trimester; may be used later in pregnancy (except paroxetine Class D).
• Precautions:
- BZDs: Advanced age, renal insufficiency, suicidal tendency, open-angle glaucoma. Sudden discontinuation increases the risk of seizures, especially with alprazolam.
- BZDs with short half-lives (e.g., alprazolam) increase the potential for dependency and protracted withdrawal symptoms; use with caution when patients with severe panic disorder are taking other CNS sedatives or with patients who have a history of substance abuse/dependence.
- Buspirone: Hepatic and/or renal dysfunction
- TCAs: Advanced age, glaucoma, benign prostate hypertrophy, hyperthyroidism, cardiovascular disease, liver disease, urinary retention, MAO inhibitor treatment
• Significant possible interactions
- BZDs (CYP inhibitors/inducers): Cimetidine, ethanol, oral contraceptives, disulfiram, levodopa, rifampin
- Buspirone: MAO inhibitors
- TCAs: Amphetamines, barbiturates, guanethidine, clonidine, epinephrine, ethanol, norepinephrine, MAO inhibitors, propoxyphene, allow 14-day washout period before starting MAOIs after TCA d/c
- SSRIs: MAO inhibitors (may cause fatal serotonin syndrome), may raise serum levels of other medications
FOLLOW-UP
PROGNOSIS
With active treatment, excellent results can often be obtained.
COMPLICATIONS
• Impaired social/occupational functioning
• Drug dependence (benzodiazepines)
• Alcohol dependence
PATIENT MONITORING
• Watch for and treat associated psychiatric disorders.
• Monitor mental status on benzodiazepines and avoid drug dependence.
• Monitor blood pressure, heart rate, and anticholinergic side effects on TCAs.
• Monitor for suicidality with SSRIs, venlafaxine, and imipramine.
REFERENCES
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association, 2000:429-484.
2. Rickels K, Moira R. Pharmacotherapy of generalized anxiety disorder. J Clin Psychiatry. 2002;63(suppl 14):9-16.
3. Lepine J. The epidemiology of anxiety disorders: Prevalence and societal costs. J Clin Psychiatry. 2002;63(suppl 14):4-8.
4. Kirkwood C, Melton S, Pharmacotherapy: A pathophysiologic approach. In: Anxiety Disorders I: Generalized Anxiety, Panic, and Social Anxiety Disorders. 6th ed. New York, NY; McGraw Hill: 2005.
5. Rickels K, Rynn M, Iyengar M, et al. Remission of generalized anxiety disorder: A review of the paroxetine clinical trials database. J Clin Psychiatry. 2006;67(1):41-47.
6. Goodman WK, Bose A, Wang Q. Treatment of generalized anxiety disorder with escitalopram: Pooled results from double-blind, placebo-controlled trials. J Affect Disord. 2005;87(2-3):161-167.
7. Mitte K, Noack P, Steil R, Hautzinger M. A meta-analytic review of the efficacy of drug treatment in generalized anxiety disorder. J Clin Psychopharmacol. 2005;25(2):141-150.
8. Briggs G. Drugs In Pregnancy And Lactation: A Reference Guide to Fetal and Neonatal Risk. 7th ed. Philadelphia, PA: Lippincott Williams  Wilkins; 2005.
ADDITIONAL READING
• Medline Plus, www.medlineplus.gov
• Mayo Clinic, www.mayoclinic.com
MISCELLANEOUS
Abbreviations: DSM-IV-R, Diagnostic and Statistical Manual of Mental Disorders, 4th edition Text Revision; TCA, tricyclic antidepressant; SSRI, selective serotonin reuptake inhibitor; CYP, cytochrome P450 enzymes; BZD, benzodiazepine

ANTITHROMBIN DEFICIENCY

2009-01-03T06:57:00.000-08:00

ANTITHROMBIN DEFICIENCY - Marc JeffreyKahn, MD
BASICS
DESCRIPTION
Antithrombin is a protease that inhibits thrombin by forming an irreversible complex. Antithrombin can also inhibit factors Xa, IXa, and XIa. This process is catalyzed by the presence of heparin. Patients deficient in antithrombin have an increased incidence of venous thrombosis including venous thrombosis. Arterial thrombosis is much less common in patients deficient in antithrombin.
• System(s) Affected: Cardiovascular; Nervous; Pulmonary; Reproductive; Hemic/Lymphatic/ Immunologic
• Synonym(s): Antithrombin III deficiency
GENERAL PREVENTION
Patients with antithrombin deficiency without thrombosis do not require prophylactic treatment.
EPIDEMIOLOGY
• Predominant age: Mean age of 1st thrombosis is in the 2nd decade
• Predominant sex: Male = Female
Incidence
4% of patients with thrombophilia
Prevalence
0.16% of normal individuals
RISK FACTORS
• Oral contraceptives, pregnancy, and the use of hormone replacement therapy (HRT) increase the risk of venous thrombosis in patients with antithrombin deficiency.
• Patients with antithrombin deficiency and another prothrombotic state such as factor V Leiden or the prothrombin 20210 mutation have increased rates of thrombosis.
ALERT
Pregnancy Considerations
Increases thrombotic risk in patients with antithrombin deficiency
Genetics
• Autosomal dominant.
• Heterozygotes have an odds ratio of venous thrombosis of 10-20.
ETIOLOGY
Many mutations in the antithrombin gene have been identified.
• Type I deficiency is characterized by low levels of antigen. Type II deficiency is found when the antithrombin molecule is dysfunctional.
• Type II deficiencies are due to mutations in either the active center of antithrombin that binds the target enzyme or the heparin binding site.
• No patients homozygous for defects in the active center have been described, suggesting that this is a lethal condition. Patients heterozygous for mutations in the heparin binding site rarely have thrombotic episodes.

DIAGNOSIS
SIGNS AND SYMPTOMS
• Deep or superficial venous thrombosis
• Recurrence rate of thrombosis is 12-17% per year.
TESTS
Lab
• Antithrombin levels in the presence of heparin
• Anti-thrombin-heparin cofactor assay
• Drugs that may alter lab results: Heparin and asparaginase can lower antithrombin levels.
• Disorders that may alter lab results
- Liver disease, DIC, nephritic syndrome, and preeclampsia reduce antithrombin levels.
- Acute thrombosis can lower antithrombin levels.
DIFFERENTIAL DIAGNOSIS
• Factor V Leiden
• Protein C deficiency
• Protein S deficiency
• Dysfibrinogenemia
• Dysplasminogenemia
• Homocysteinemia
• Prothrombin 20210 mutation
• Elevated factor VIII levels
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Routine anticoagulation for asymptomatic patients with antithrombin deficiency is not recommended. (1)[A]
• Patients with antithrombin deficiency and a 1st thrombosis should be anticoagulated initially with unfractionated heparin followed by oral anticoagulation with warfarin. (1)[A]
• The role of family screening for antithrombin deficiency is unclear, because most patients with this mutation do not have thrombosis. Screening may be considered for women considering using oral contraceptives or for pregnant women with a family history of factor protein S deficiency. (1)[C]
Diet
No restrictions
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Heparin initial bolus of 80 U/kg followed by infusion of 18 U/kg/h. Frequent monitoring of the PTT is important as nearly 1/2 of patients deficient in antithrombin require more than 40,000 U of heparin daily to adequately prolong the PTT. (1)[C] After the INR is 2-3, heparin can be stopped after 5 total days of therapy. (1)[A]
• Oral anticoagulant following the initial administration of heparin. Warfarin (Coumadin) 5 mg PO per day and adjusted to INR of 2-3. Patients should be maintained on warfarin for at least 6 months. (1)[A]
• Recurrent thrombosis requires indefinite anticoagulation. (1)[A]
• Contraindications
- Active bleeding precludes anticoagulation; risk of bleeding is a relative contraindication to long-term anticoagulation.
• Precautions
- Observe patient for signs of embolization, further thrombosis, or bleeding.
- Avoid IM injections.
- Periodically check stool and urine for occult blood and monitor CBCs including platelets.
- Heparin-thrombocytopenia and/or paradoxical thrombosis with thrombocytopenia
• Significant possible interactions
- Agents that intensify the response to oral anticoagulants: Alcohol, allopurinol, amiodarone, anabolic steroids, androgens, many antimicrobials, cimetidine, chloral hydrate, disulfiram, all NSAIDs, sulfinpyrazone, tamoxifen, thyroid hormone, vitamin E, ranitidine, salicylates, acetaminophen
- Agents that diminish the response to oral anticoagulants: Aminoglutethimide, antacids, barbiturates, carbamazepine, cholestyramine, diuretics, griseofulvin, rifampin, and oral contraceptives
Second Line
• Argatroban 0.4-0.5 mcg/kg/min. Case reports describing the use of the direct thrombin inhibitor in patients with antithrombin deficiency have been published. (2)[C]
• Antithrombin III (ATnativ, Thrombate III) 50-100 IU/min IV titrated to antithrombin level desired. Precise role in therapy remains unclear. (1)[C]
• LMWH is difficult to manage in this population. (1)[C]
FOLLOW-UP
PROGNOSIS
The odds ratio of thrombosis in a patient with antithrombin deficiency is much higher than in patients with other thrombophilic conditions. The recurrence rate is similarly high. There is no difference in clinical severity between patients with type I defects and type II mutations.
COMPLICATIONS
Recurrent thrombosis (requires indefinite anticoagulation)
PATIENT MONITORING
Warfarin requires periodic (monthly after initial stabilization) monitoring of the INR.
REFERENCES
1. Vinazzer H. Hereditary and acquired antithrombin deficiency. Semin Thromb Hemost. 1999;25(3): 257-263.
2. Dager WE, Gosselin RC, Owings JT. Argatroban therapy for antithrombin deficiency and mesenteric thrombosis: Case report and review of the literature. Pharmacotherapy. 2004;24(5): 659-663.
3. Kottke-Marchant K, Duncan A. Antithrombin deficiency: Issues in laboratory diagnosis. Arch Pathol Lab Med. 2002;126(11):1326-1336.
MISCELLANEOUS
See also: Thrombosis; Deep Vein (DVT); Protein C Deficiency; Protein S Deficiency; Prothrombin 20210 (Mutation); Factor V Leiden

ANTI PHOSPHOLIPID ANTIBODY SYNDROME

2009-01-02T20:06:00.000-08:00

ANTI-PHOSPHOLIPID ANTIBODY SYNDROME - Christopher S.Manasseh, MD
BASICS
DESCRIPTION
• An autoimmune thrombotic syndrome characterized by the presence of antiphospholipid antibodies in association with either recurrent venous or arterial thromboembolic events or repeated fetal loss
• Types
- Primary
 Occurs in patients without clinical evidence of another autoimmune disease
- Secondary
 Occurs in association with another disease such as systemic lupus erythematosus (SLE)
- Catastrophic antiphospholipid syndrome
 Differs from primary and secondary types in the caliber of vessels affected. Venous or arterial thrombosis of large vessels is less common, and patients present with acute thrombotic microangiopathy, kidney being the most commonly affected organ.
 Disseminated intravascular coagulation which does not occur in primary or secondary forms is seen in up to 25% of patients with the catastrophic type.
• Synonym(s): Hughes syndrome
ALERT
Geriatric Considerations
Atherosclerosis and cancer are more frequent causes of thrombosis than is antiphospholipid antibody syndrome.
Pregnancy Considerations
• Increased frequency of recurrent fetal loss
• Increased risk of premature delivery due to pregnancy related hypertension and uteroplacental insufficiency
GENERAL PREVENTION
In pregnant women with h/o recurrent fetal loss, use low dose unfractionated heparin 5000 U SQ b.i.d.
In all women with the syndrome and previous pregnancy loss, aspirin 325 mg/day may provide protection against future thrombosis.
Modification of secondary risk factors for atherosclerosis include control of hypertension, diabetes, hyperlipidemia, and smoking cessation.
EPIDEMIOLOGY
1/2 of all patients with the syndrome have the primary form of the disease.
Incidence
• 15% of women with recurrent pregnancy loss have this syndrome
• 63% of patients have at least 1 valvular abnormality on echocardiogram
Prevalence
1-5% of otherwise young healthy adults have antiphospholipid antibodies
50-70% of patients with SLE who have the antiphospholipid antibodies may develop this syndrome
RISK FACTORS
• Smoking
• Oral contraceptive use
• Surgery
• Immobilization
• Pregnancy
PATHOPHYSIOLOGY
Any organ can be involved, and the extent of involvement depends on the
• Nature and size of vessel involved
• Acuteness or chronicity of the thrombotic process
ETIOLOGY
Antiphospholipid antibodies promote thrombosis by any of the following hypotheses
• Activation of endothelial cells
• Oxidant-mediated injury of the vascular endothelium
• Interference with the phospholipid binding proteins involved in the regulation of coagulation
ASSOCIATED CONDITIONS
• SLE
• Malignant hypertension
• Nephrotic syndrome

DIAGNOSIS
SIGNS AND SYMPTOMS
• Arthralgia
• Livedo reticularis
History
• Family history of rheumatic illness
• Personal history of thrombosis
Physical Exam
Look for deep vein thrombosis of the legs.
Most common manifestation of the syndrome
TESTS
• ELISA test for anticardiolipin antibodies
• Clotting test for lupus anticoagulant
Lab
• Thrombocytopenia
• Leukopenia
Diagnostic Criteria
• The presence of at least ONE of the following clinical criteria
- Vascular thrombosis
 1 or more clinical episodes of arterial, venous, or small vessel thrombosis, occurring within any tissue or organ
- Complications of pregnancy
 1 or more unexplained deaths of morphologically normal fetuses at or after the 10th week of pregnancy OR
 1 or more premature births of morphologically normal neonates at or before the 34th week of pregnancy OR
 3 or more unexplained consecutive spontaneous abortions before the 10th week of pregnancy
• AND presence of at least ONE of the following laboratory criteria
- Anticardiolipin antibodies
 Anticardiolipin IgG or IgM antibodies present at moderate or high levels in the blood on 2 or more occasions at least 6 weeks apart
- Lupus anticoagulant antibodies
 Detected in the blood on 2 or more occasions at least 6 weeks apart
Pathological Findings
• Acute changes
- Capillary congestion
- Non-inflammatory fibrin thrombi
• Chronic changes
- Ischemic hypoperfusion
- Atrophy and fibrosis
DIFFERENTIAL DIAGNOSIS
• Other conditions that cause thrombotic microangiopathy, such as
- Hemolytic-uremic syndrome
- Thrombotic thrombocytopenic purpura
• Other thrombophilic conditions, such as
- Deficiency of protein C, protein S
- Deficiency of antithrombin III
- Mutation of factor V Leiden
- Prothrombin gene mutation
- Homocysteinemia
MEDICATION (DRUGS)
First Line
Warfarin treatment of moderate intensity (to achieve an international normalized ratio (INR) of 2-2.9) significantly reduces the rate of recurrent thrombosis.
• Duration of treatment is lifelong.
Second Line
Corticosteroids and azathioprine for treatment of symptoms of lupus in patients with secondary form of the syndrome
SPECIAL THERAPY
In patients who develop new thromboses despite moderate intensity anticoagulant therapy and for patients with catastrophic antiphospholipid syndrome
• Plasmapheresis
• IV immune globulin
FOLLOW-UP
PROGNOSIS
• Pulmonary hypertension, neurologic involvement, myocardial ischemia, nephropathy, gangrene of extremities, and catastrophic APS are associated with a worse prognosis.
• Most patients experience recurrences months or years after the initial event.
• Mortality rate is ~50% in patients presenting with the catastrophic type, and death is due to multi-organ system failure.
COMPLICATIONS
Discontinuation of warfarin results in increased risk of thrombosis (even death), particularly in the 1st 6 months after stopping treatment.
PATIENT MONITORING
As warfarin therapy is lifelong, patients need to have regular monitoring to maintain INR in the therapeutic range (between 2 and 2.9).
REFERENCES
1. Lockshin M. Antiphospholipid antibody syndrome. In: Ruddy S, Harris ED, Sledge CB, ed. Kelley's Textbook of Rheumatology. Philadelphia: Saunders Company; 2001;1145-1152.
2. Erkan D, Yazici Y, Sobel R, Lockshin MD. Primary antiphospholipid syndrome. Functional outcome after 10 years. J Rheumatol. 2000;27:2817-2821.
3. Levine JS, Branch DW. The antiphospholipid syndrome. N Eng J Med. 2002;10:752-759.
4. Crowther MA, Ginsberg JS, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with antiphospholipid syndrome. N Eng J Med. 2003;12:1133-1138.
ADDITIONAL READING
The decade of autoimmunity: edited by Y. Shoenfeld, publication date 1999.

ANTHRAX

2009-01-02T20:04:00.000-08:00

ANTHRAX - Benjamin L. Sapers, MD
BASICS
DESCRIPTION
• Anthrax is a highly infectious disease of animals, especially ruminants (hooved animals such as cows, goats, sheep, etc.) that is caused by the bacteria Bacillus anthracis. Cutaneous (95% of US cases); inhalational, and gastrointestinal forms can be transmitted to man by contact with the animals or their products.
• Synonym(s) for skin anthrax: Charbon; Malignant pustule; Siberian ulcer; Malignant edema; Splenic fever; Milzbrand; Ragpicker disease
• Synonym(s) for chest anthrax: Woolsorter disease
GENERAL PREVENTION
• Anthrax vaccine protects against all forms of anthrax and is as safe as other vaccines, according to the Food and Drug Administration, the Centers for Disease Control and Prevention, and the National Academy of Sciences. A 2005 review by the Cochrane Infectious Disease Group concluded that the anthrax vaccine is effective in reducing the risk of contracting anthrax and has a low rate of adverse effects (1)[A].
• Vaccine is given in 6 doses (0, 2, and 4 weeks, and 6, 12, and 18 months) plus annual boosters.
- If you get behind schedule, don't start the series over; begin where you left off (delays don't reduce the resulting protection).
- Redness up to 1 inch (1 cm) wide occurs in 30% of men and 60% of women, and redness or other reactions >5 inches (4 cm) occur in ~1% of people (both male and female).
- Anthrax vaccine often causes a nodule under the skin where the vaccine is injected; this can last from 2-3 months. These nodules eventually resolve.
- The Advisory Committee on Immunization Practices recommends vaccination for the following groups
 Persons who work directly with the organism in the laboratory
 Persons who work with imported animal hides or furs in areas where standards are insufficient to prevent exposure to anthrax spores
 Persons who handle potentially infected animal products in high-incidence areas
 Military personnel deployed to areas with high risk for exposure to organisms (when used as a biologic warfare weapon)
 Pregnant women should be vaccinated for anthrax only if absolutely necessary.
• Patients with a likely exposure history but no symptoms are candidates for postexposure prophylaxis with either ciprofloxacin 500 mg PO b.i.d. or doxycycline 100 mg PO b.i.d.
EPIDEMIOLOGY
• Cutaneous (skin): 95% of cases in the US; cases of cutaneous anthrax without occupational risk should raise concern for a terrorist attack. About 5-20% of untreated cases result in death.
• Gastrointestinal (GI): Very rare in the US (no documented case in the 20th century).
• Inhalational (chest) anthrax is very rare in US; must be considered a bioterrorist event in US until proven otherwise (the last US occupational case occurred in 1976). Death results in 99% of untreated cases, and in 45-80% of patients with severe symptoms who are treated in a state-of-the-art facility.
• Anthrax is most common in agricultural regions, where it occurs in animals. These regions include the Middle East, Asia, Southern and Eastern Europe, Africa, South and Central America, and the Caribbean.
RISK FACTORS
• Contact with infected animals or their products
• Bioterrorist event
PATHOPHYSIOLOGY
• Bacillus anthracis is a spore-forming, gram-positive bacterium found in the soil worldwide. The word anthracis is derived from a Greek word meaning "coal," which is used to describe the cutaneous form of the disease that leads to a characteristic black lesion.
• B. anthracis has 3 known virulence factors: An antiphagocytic capsule and 2 protein toxins (known as edema factor and lethal factor).
- The capsule provides resistance to phagocytosis.
- Lethal factor and edema factor are named for the effects they induce when injected into experimental animals.
- A protein called protective antigen binds to the host cell's surface; when cleaved by a protease on the cell surface it creates a binding site to which the lethal factor and edema factor can bind; protective antigen is required for the action of the 2 protein toxins.
• B. anthracis spores introduced into the host are ingested at the exposed site by macrophages and then germinate into vegetative forms that produce the virulence factors.
ETIOLOGY
• Skin: Occurs when B. anthracis enters the skin through a cut or abrasion during the handling of animal products (such as meat, wool, or hides infected with B. anthracis)
• GI: Ingestion of bacillus-contaminated meat
• Chest: Inhalation of aerosolized B. anthracis spores

DIAGNOSIS
SIGNS AND SYMPTOMS
• Skin: Begins as a pruritic red-brown papule that enlarges with peripheral erythema, vesiculation, and induration, followed by black eschar formation within 7-10 days of the initial lesion. The papule, blister, and eschar are painless, and cutaneous symptoms may be accompanied by fever, malaise, and headache. A black eschar with massive edema is nearly pathognomonic for cutaneous anthrax.
• GI: Presents as 1 of 2 distinct syndromes  oropharyngeal and abdominal. Oropharyngeal syndrome presentation can include fever, edema, ulcer, severe sore throat, and lymphadenopathy resulting in marked unilateral or bilateral neck swelling. Abdominal syndrome may present with fever, malaise, hematemesis, anorexia, severe abdominal pain, and hematochezia or melena.
• Chest: Biphasic presentation, with initial phase featuring nonspecific influenzalike symptoms such as low-grade fever, chills, headache, nonproductive cough, diaphoresis, malaise, chest discomfort, nausea, vomiting, diarrhea, and abdominal pain. This initial phase is followed by the 2nd fulminant phase that includes abrupt onset of high fever, severe dyspnea, hypoxia, hypotension, and death.
History
• Skin: Crucial clinical clues are the rapid evolution of symptoms, lack of pain, occasional massive edema, and the near pathognomonic black eschar. Incubation period is usually immediate but may last up to 1 day.
• GI: Incubation period usually 1-7 days; 2-4 days after onset of symptoms, ascites develop as abdominal pain decreases. Shock and death occur within 2-5 days after onset of symptoms.
• Chest: Incubation period is usually 1 week, but may be as long as 2 months. 2nd portion of the biphasic presentation begins 1-5 days after onset of initial symptoms. There may be a 1-3 day period of improvement after the 1st phase and before the 2nd phase begins. Shock and death occur within 24-36 hours after onset of the 2nd phase.
Physical Exam
• Skin: Red-brown papule, vesicles, or black eschar
• GI: Acute abdomen with rebound tenderness may occur. Ascites present later in course
• Chest: Rhonchi may be present.
TESTS
Lab
Gram stain and culture. A presumptive diagnosis can be made if Gram-positive rods are present that are nonmotile, nonhemolytic, and encapsulated (usually seen with India ink). If antibiotics have been given for >24 hours, perform immunohistochemical staining and/or polymerase chain reaction.
Imaging
• Widened mediastinum on chest radiograph may be present in inhalational anthrax.
• Pleural effusions frequently present in chest anthrax; infiltrates are rare.
• GI: Mesenteric adenopathy on CT scan likely.
DIFFERENTIAL DIAGNOSIS
Skin
Cellulitis
Brown recluse spider bite
Cat-scratch disease
Rat bite fever
Rickettsial spotted fever
Carbuncle
Cowpox
Bullous erysipelas
Tularemia vasculitides
Ecthyma gangrenosum
Orf (a transmissible viral disease of goats and sheep)
TREATMENT
GENERAL MEASURES
Chest and GI anthrax is not known to spread from person to person, so communicability concerns are not an issue during management of the patient. For skin anthrax, avoid contact with the wound or wound drainage.
MEDICATION (DRUGS)
First Line
• Skin: Ciprofloxacin 500 mg PO b.i.d. for 60 days or doxycycline 100 mg PO b.i.d. for 60 days. If systemic involvement, massive edema, or lesions on the head or neck, follow treatment recommendation per inhalational anthrax (2)[C].
• Chest and GI: IV ciprofloxacin 400 mg q12h or doxycycline 100 mg q12h AND 1 or 2 additional antimicrobials such as rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin. May switch to PO when clinically appropriate. Must complete 60-day course (combined PO and IV) (2)[C].
Second Line
Patients being treated for anthrax may also benefit from vaccination as part of their regimen (3)[C].
FOLLOW-UP
PROGNOSIS
• Skin: Death in 5-20% of untreated cases.
• GI: Mortality rates as high as 50% have been reported.
• Chest: Death in 99% of untreated cases.
PATIENT MONITORING
Must monitor patient for 60 days to ensure completion of the treatment course
REFERENCES
1. Jefferson T, Demicheli V, Deeks J, et al. Vaccines for preventing anthrax. [Systematic Review] Cochrane Infectious Diseases Group. Cochrane Database of Systematic Rev. 1, 2006.
2. Centers for Disease Control and Prevention. Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep. 2001;50(42):909-919. Erratum in: MMWR Morb Mortal Wkly Rep. 2001;50(43):962.
3. Centers for Disease Control and Prevention. Use of anthrax vaccine in the United States, ACIP Recommendations. MMWR Recommendations  Reports. 2000;49(RR-15):1-20.
ADDITIONAL READING
• The anthrax vaccine immunization program. http://www.anthrax.mil
• Centers for Disease Control and Prevention, Emergency Preparedness and Response. http://www.bt.cdc.gov/agent/anthrax/
• Durning SJ, Roy MJ. Anthrax. In: Roy MJ, ed. Physician's Guide to Terrorist Attack. Totowa, NJ: Humana Press Inc.; 2003.

ANOREXIA NERVOSA (AN)

2009-01-02T19:46:00.000-08:00

ANOREXIA NERVOSA (AN) - Mary Muscari, PhD, RN, CRNP, CS
BASICS
DESCRIPTION
• Refusal to maintain normal body weight, with associated fear of weight gain, body image disturbance, and amenorrhea
• Restricting and binge-eating/purging subtypes
• System(s) Affected: Cardiovascular; Endocrine; Metabolic; Gastrointestinal; Nervous; Reproductive
GENERAL PREVENTION
Encourage rational attitude about nutrition and weight, minimize weight-related criticism and teasing, moderate overly high self-expectations, enhance self-esteem
EPIDEMIOLOGY
• Predominant age at onset: 13-18 years
• Predominant sex: Female > Male (20:1)
• Global distribution
Incidence
8-19 women, 2 men per 100,000 per year
Prevalence
1% in women, 0.1% in men
RISK FACTORS
• Female gender
• Perceived body image distortions
• Perfectionism, obsessionality, rigidity
• Negative self-evaluation
• Academic and other achievement pressure
• Participation in sports or artistic activities that emphasize leanness or involve subjective scoring
- Ballet, running, wrestling, figure skating, gymnastics, cheerleading, weight lifting
• Parental psychiatric disorder
Genetics
• Underlying genetic vulnerability likely, but not well understood
- 1st-degree female relative with eating disorder increases risk 6- to 10-fold.
PATHOPHYSIOLOGY
Complex relationship between biologic, psychological, and social factors that results in an unrealistic perception of fatness. Subsequent malnutrition leads to disorder of multiple organs.
ETIOLOGY
• Serotonin neuronal systems are implicated.
• Multifactorial withpsychological, biological, genetic, environmental, and social factors
ASSOCIATED CONDITIONS
• Mood disorder
• Social phobia, obsessive-compulsive disorder
• Substance abuse disorder
• High rates of cluster C personality disorders

DIAGNOSIS
SIGNS AND SYMPTOMS
• Onset may be insidious or stress related
• Amenorrhea (primary or secondary)
• Report feeling fat even when emaciated
• Preoccupation with body size, weight control
• Elaborate food preparation and eating rituals
• Extensive exercise
• Weakness, fatigue, cognitive impairment
• Hypothermia, cold intolerance
• Constipation, bloating, early satiety
• Dry skin, scalp hair loss, peripheral edema
• Lanugo hair on extremities, face, and trunk
• Growth arrest, delayed puberty
• Hypotension, bradycardia, murmurs
• Decreased bone density, fractures
History
Ascertain fear of weight gain and/or distorted body image.
Physical Exam
• Often normal
• Vital signs: Bradycardia, orthostatic hypotension, body weight 85% expected
• Cardiac: Dysrhythmias, midsystolic click of mitral valve prolapse
• Skin/extremities: Dry, lanugo, hair loss, edema
• Neurologic and abdominal exams: To rule out other causes of weight loss and vomiting
TESTS
Lab
• No specific test for AN. Most findings are related directly to starvation, dehydration
- All findings may be within normal limits.
• Low serum leuteinizing hormone, follicle-stimulating hormone; low T4 with normal TSH
• Abnormal liver enzymes
• Altered blood urea nitrogen, creatinine clearance; electrolyte disturbances
• Hypoglycemia, hypercholesterolemia, hypercortisolemia, hypophosphatemia
• Low sedimentation rate
• Anemia, leukopenia, thrombocytopenia
• 12-lead ECG to assess for prolonged QT
Imaging
Dual-energy x-ray absorptiometry (DEXA) of bone only if underweight for >6 months to assess for diminished bone density
Diagnostic Procedures/Surgery
• DSM-IV-TR criteria
- Refusal to maintain body weight at or above a minimally normal weight for age, height
- Intense fear of gaining weight even though underweight
- A disturbance in the way body weight/shape is experienced; undue influence of body on self-evaluation or denial of seriousness of low body weight
- Specific types
 Restricting: Not engaged in binge-eating or purging behaviors
 Binge-eating/purging type: Regularly engages in binge-eating or purging behaviors (see Bulimia information related to these behaviors)
• Screening tools: SCOFF questionnaire, Eating disorder Screen for Primary Care (ESP), Eating Attitudes Test (EAT), Eating Disorder Inventory (EDI)
Pathological Findings
• Osteoporosis/osteopenia, pathologic fractures
• Sick euthyroid syndrome
• Cardiac impairment
DIFFERENTIAL DIAGNOSIS
• Hyperthyroidism,adrenal insufficiency
• Inflammatory bowel disease
• Immunodeficiency, chronic infections
• Malabsorption, diabetes
• CNS lesion
• Bulimia; body dysmorphic disorder
• Depressive disorders with loss of appetite
• Anxiety disorder, food phobia
• Conversion disorder, schizophrenic disorder
ALERT
AN may exist concurrently with chronic medical disorders, such as diabetes, cystic fibrosis.
TREATMENT
GENERAL MEASURES
• Initial treatment goal geared to weight restoration; most are managed as outpatients
• Outpatient treatment
- Interdisciplinary team (primary care physician, mental health professional, nutritionist) (1,2)[B,C]
- Average weekly weight gain goal: 0.5-1.0 kg (1)[C] with stepwise increase in calories
- Cognitive behavioral and/or family-based therapy (2,3)[B]
- Focus on health, not weight gain alone.
- Build trust, treatment alliance,
- Involve patient in establishing diet and exercise goals.
- Challenge fear of uncontrolled weight gain; help the patient to recognize feelings that lead to disordered eating.
- In chronic cases, goal may be to achieve a safe weight rather than a healthy weight.
• Inpatient treatment
- If possible, admit to specialized eating disorders unit (4)[C]
- Monitor vital signs, cardiac function, watch for edema, rapid weight gain (fluid overload)
- Initial bed rest with supervised meals may be necessary.
- Stepwise increase in activity
- Tube feeding or total parental nutrition used only as last resort
- Supportive symptomatic care as needed
Diet
• Goal is stabilization at a healthy weight on a balanced diet with normal eating pattern
• Diminished ruminations about calories, weight; increased enjoyment
Activity
• Monitor activity.
• Stepwise increase as patient gains weight
• Focus on enjoyable activities rather than goal-oriented ones.
MEDICATION (DRUGS)
First Line
• No medications are available that effectively treat patients with AN, but antidepressants may benefit those with comorbid depression (5,6)[C].
• Selective serotonin-reuptake inhibitors such as fluoxetine (Prozac): 10-60 mg may
- Help prevent relapse after weight gain
- Treat comorbid depression or obsessive-compulsive disorder (1,4,6)[C]
- Attend to black box warnings concerning antidepressants and conduct appropriate informed consent if antidepressants are prescribed
Second Line
• Management of osteopenia
- Elemental calcium 1200-1500 mg/d plus MVI containing 800 IU of vitamin D (2,4)[C]
- No indication for bisphosphonates in AN (2)[C]
- Weak evidence for use of HRT (2)[C]
- Psyllium (Metamucil) preparations (1 tbsp) to prevent constipation
FOLLOW-UP
DISPOSITION
Admission Criteria
• Suggested physiologic values: Heart rate 40 bpm, BP 90/60, symptomatic hypoglycemia, potassium 3 mmol/L, temperature 97.0F (36.1C), dehydration, other cardiovascular abnormalities, weight 75% of the expected weight, rapid weight loss, lack of improvement while in outpatient therapy
• Suggested psychological indications: Poor motivation/insight, lack of cooperation with outpatient treatment, inability to eat, need for nasogastric feeding, suicidal plan or intent, severe coexisting psychiatric disease, problematic family environment
ALERT
Pediatric Considerations
• Children often present with nausea, abdominal pain, fullness, and inability to swallow.
• Additional indications for hospitalization: Heart rate 50 bpm, orthostatic BP, hypokalemia or hypophosphatemia, rapid weight loss even if weight not 75% below normal
Geriatric Considerations
Late-onset AN (>50) may be long-term disease, or triggered by death of loved one, marital discord, or divorce.
Discharge Criteria
Lower relapse rate when discharged at expected healthy weights
PROGNOSIS
• Prognosis: ~50% recover; 25% improved; 25% chronically ill
• Mortality: 5-7%
COMPLICATIONS
• Refeeding syndrome
• Cardiac arrhythmia; cardiac arrest
• Cardiomyopathy, congestive heart failure
• Delayed gastric emptying, necrotizing colitis
• Seizures, Wernicke encephalopathy, peripheral neuropathy, cognitive deficits
• Osteopenia, osteoporosis
Pregnancy Considerations
• Fertility may be affected.
• Increased risk for miscarriage, operative delivery, congenital malformations, and low-birth-weight infants; should be managed as high risk
PATIENT MONITORING
• Level of exercise activity
• Weigh weekly until stable, then monthly.
• Depression, self-esteem, suicidal ideation
REFERENCES
1. NICE. Eating disorderscore interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders. NICE Clinical Guideline no 9. London: NICE, 2004 (accessed 15 Feb 2006).
2. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Eating Disorders, 3rd ed. 2006, June (accessed Dec 10, 2006).
3. Hay P, Bacaltchuk J, Claudino A, Ben-Tovim D, et al. Individual psychotherapy in the outpatient treatment of adults with anorexia. Cochrane Database Syst Rev. 2003;(4):CD003909.
4. Yager J, Anderson AE. Anorexia nervosa. N Engl J Med. 2005;353:1481-1488.
5. Berkman ND, Bulik CM, Brownley KA, et al. Management of eating disorders. Evidence report/technology assessment No. 135. (Prepared by the RTI International-University of North Carolina Evidence-Based Practice Center under Contract No. 290-02-0016.) AHRQ Publication No. 06-E010. Rockville, MD: Agency for Healthcare Research and Quality, April 2006.
6. Claudino A, Hay P, Lima M, et al. Antidepressants for anorexia nervosa. Cochrane Database Sys Rev. 2006;(1):CD04365.

ANORECTAL FISTULA

2008-12-31T06:24:00.000-08:00

ANORECTAL FISTULA - Timothy L.Black, MD
BASICS
DESCRIPTION
Inflammatory track with one opening in the anal canal and another in perianal skin. Fistulas occur spontaneously or secondary to perirectal abscess. Most fistulas originate in the anal crypts at the anorectal junction.
• Goodsall's rule
- If external opening is anterior to an imaginary line drawn horizontally through anal canal, fistula usually runs directly into anal canal.
- If external opening is posterior to line, fistula usually curves to posterior midline of anal canal.
- For Goodsall's rule: Anterior fistulae, PPV is ~70%, for Posterior fistulae, PPV is ~40%.
- In children, track is usually straight.
• Classification (1)[C]
- Intersphincteric: Fistula is confined to the intersphincteric plane (most common).
- Transsphincteric: Fistula connects intersphincteric plane with ischiorectal fossa by perforating the external sphincter.
- Suprasphincteric: Fistula connects intersphincteric plane with ishiorectal fossa but loops over external sphincter.
- Extrasphincteric: Fistula connects rectum to perineal skin but passes external to sphincter.
• System(s) Affected: Gastrointestinal; Skin/Exocrine
• Synonym(s): Fistula-in-ano; Anal fistula
ALERT
Geriatric Considerations
Constipation is a common complication.
Pediatric Considerations
• Most common in infants
• More frequent in males
GENERAL PREVENTION
Prevention or prompt treatment of anorectal abscess
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
Common
RISK FACTORS
• Injection of internal hemorrhoids, puncture wound from eggshells or fish bones, foreign objects, enema tip injuries
• Ruptured anal hematoma
• Prolapsed internal hemorrhoid
• Acute appendicitis, salpingitis, diverticulitis
• Inflammatory bowel disease (chronic ulcerative colitis, Crohn disease)
• Previous perirectal abscess
• Radiation treatment to perineum/pelvis
• Trauma, either internal or external
• Carcinoma
ETIOLOGY
• Erosion of anal canal
• Extension from infection from a tear in lining of anal canal
• Infecting organism is commonly Escherichia coli
ASSOCIATED CONDITIONS
• Possibly associated with penetrating injury, intestinal tuberculosis, ulcerative colitis
• Hidradenitis suppurativa
• Crohn disease

DIAGNOSIS
SIGNS AND SYMPTOMS
• Constant or intermittent drainage or discharge
• Firm tender perianal lump
• External anal sphincter pain during and after defecation
• Spasm of external anal sphincter during and after defecation
• Anal bleeding
• Discoloration of skin surrounding fistula
• Fistulous opening frequently granulose or scarred
• Possible fever
• Recurrent anorectal abscesses in identical locations
History
• History of perianal drainage
• History of perianal pain
• History of recurrent perianal abscesses
Physical Exam
• Perineal or perianal draining orifice
• Recurrent perianal abscesses in identical location
• Small palpable lesion sometimes identified on rectal exam at level of anal crypts
TESTS
Lab
• Complete blood count (usually not indicated)
• Prometheus first step serology for inflammatory bowel disease (if Crohn disease suspected)
• Consider RPR for recurrent fistulas in sexually active patients.
Imaging
• Lower gastrointestinal series if inflammatory bowel disease suspected
• Pelvic MRI or endorectal ultrasound may be useful in complex or recurrent fistulas
Diagnostic Procedures/Surgery
• Proctoscopy
• Sigmoidoscopy
• Probe inserted into tract to determine its course (be careful not to create an artificial opening)
• Injection of dilute methylene blue into abscess cavity may be helpful in demonstrating fistula (1)[C]
Pathological Findings
• Fistulous tract may be simple or multiple
• Fistulous tract has primary opening in anal crypt; secondary opening in anal skin, para-anal skin, perineal skin, or in rectal mucus membrane
• Anal sinus: Opens in anal crypt
• Termination of sinus is blind and located in para-anal or pararectal tissue.
DIFFERENTIAL DIAGNOSIS
• Pilonidal sinus
• Perianal abscess
• Urethroperineal fistulas
• Ischiorectal abscess
• Submucous or high muscular abscess
• Pelvirectal abscess (rare)
• Rule out: Crohn disease; carcinoma; retrorectal tumors
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient surgery
• Sitz baths 3-4 times per day until definitive surgery
Diet
Clear liquid diet until gastrointestinal function returns
Activity
Resume work and normal activity as soon as possible.
MEDICATION (DRUGS)
• Broad-spectrum antibiotic if active infection
- Cephalexin (Keflex)
- Cefadroxil (Duricef)
- Ampicillin-sulbactam (Unasyn)
- Amoxicillin-clavulanate (Augmentin)
• Stool-softening laxative
• Contraindications
- Refer to manufacturer's literature
• Precautions
- Refer to manufacturer's literature
• Significant possible interactions
- Refer to manufacturer's literature
SURGERY
• Fistulotomy
- Surgical incision of entire length of fistula (unroofing) (2)[A]
- Mucosal tract should be cauterized or curetted
- Sphincterotomy
• Fistulectomy
- Complete excision of tract (rarely indicated, because of extensive tissue loss)
- Sphincterotomy
• Consider Seton stitch placement (especially for suprasphincteric or transsphincteric fistulas). (2)[A]
• Endorectal advancement flap closure for complex fistulas. (2)[A]
• General anesthesia or regional anesthesia usually required (usually done as outpatient procedure in children)
• Consider use of fibrin glue in selected cases of anal fistulas (2)[A], (3)[C]
• Fistulas in Crohn Disease (2)[A]
- Asymptomatic fistulas may not need treatment.
- Simple fistulas treated with unroofing
- Complex fistulas treated with advancement flap or long term setons
- May require a stoma
• Postoperative: Sitz baths
• Avoid constipation.
FOLLOW-UP
PROGNOSIS
• Surgical results usually excellent
• Postoperative healing
- 4-5 weeks for perianal fistulas
- 12-16 weeks for deeper fistulas
• Postoperative healing may occur within 2-3 weeks in children.
• Recurrence rates 2-9% in simple fistulas (2)[A]
COMPLICATIONS
• Constipation (urge to defecate may be suppressed due to pain)
• Rectovaginal fistula
• Partial incontinence of fecal material if sphincter is divided
• Delayed wound healing
• Low-grade carcinoma may develop in long-standing fistulas.
• Recurrent anorectal fistula if fistula is incompletely opened or excised
• Chronic intermittent infections
• Sepsis (rarely)
PATIENT MONITORING
Frequent follow-up examinations following surgery to ensure complete healing and assess continence
REFERENCES
1. Townsend C, Beauchamp RD, Evers BM, et al., eds. Sabiston Textbook of Surgery, 17th ed. Philadelphia: Elsevier Saunders; 2006.
2. Whiteford MH, Kilkenny J, Hyman N, et al. Practice parameters for the treatment of perianal abscess and fistula-in-ano (Revised). Dis Colon Rectum. 2005;48:1337-1342.
3. Hammond TM, Grahn MF, Lunniss PJ. Fibrin glue in the management of anal fistulae. Colorectal Dis. 2004;6:308-319.

ANORECTAL ABSCESS

2008-12-31T06:21:00.000-08:00

ANORECTAL ABSCESS - Timothy L. Black, MD
BASICS
DESCRIPTION
• Localized induration and fluctuance due to inflammation of the soft tissue near the rectum or anus
• 80% are perianal, the remainder are intrasphincteric or supra-levator (1)[C]
• System(s) Affected: Gastrointestinal; Skin/Exocrine
ALERT
Geriatric Considerations
A high pelvirectal abscess may cause no symptoms except lower abdominal pain and fever.
Pediatric Considerations
Common in first year of life
GENERAL PREVENTION
• Avoid constipation.
• Don't use enemas.
• Avoid rectal temperatures or medicines in immunocompromised patients.
EPIDEMIOLOGY
• Predominant age: All ages (most common in infants) (2)[C]
• Predominant sex: Male > Female (4:1)
Incidence
Common
RISK FACTORS
• Inciting trauma
- Injections for internal hemorrhoids
- Enema tip abrasions
- Puncture wounds from eggshells or fish bones
- Foreign objects
- Prolapsed hemorrhoid
• Inflammatory bowel disease
• Chronic granulomatous disease
• Immunodeficiency disorders
• Hematologic malignancies (5-8% of these patients will have abscess at some time)
• Diabetes
• Chronic medical immunosuppression
ETIOLOGY
• Bacterial invasion of the anal glands found in the intersphincteric space, which may begin with an abrasion or tear in lining of anal canal, rectum, or perianal skin
• Organisms (usually mixed):
- Escherichia coli
- Proteus vulgaris
- Streptococci
- Staphylococci
- Bacteroides
- Pseudomonas aeruginosa
ASSOCIATED CONDITIONS
• Crohn's disease
• Other inflammatory disease (e.g., appendicitis, salpingitis, diverticulitis)
• Possibly perianal hidradenitis suppurativa, or HIV infection in patients with recurring perianal or ischiorectal abscesses

DIAGNOSIS
SIGNS AND SYMPTOMS
• Perirectal swelling for superficial abscesses
• Perirectal redness
• Perirectal tenderness
• Perirectal throbbing pain
• Fever and other toxic symptoms with deep abscesses
• If abscess is not accompanied by external swelling, digital rectal exam will reveal a swollen tender mass.
• Pain on defecation
Physical Exam
Digital rectal examination is mandatory
TESTS
Lab
Complete blood count: Leukocytosis
Imaging
• Barium enema (rarely needed)
• CT scan of pelvis and perineum indicated if horseshoe or ischiorectal abscess suspected (3)[C]
Diagnostic Procedures/Surgery
Only indicated if diagnosis in doubt
• Sigmoidoscopy: Rule out unusual causes
• Proctoscopy: Redness, induration of anus; tender mass
Pathological Findings
• Inflammation of anal mucosa
• Pus
• Inflammatory tissue
DIFFERENTIAL DIAGNOSIS
• Carcinoma
• Retrorectal tumors
• Crohn's disease
• Primary lesions of syphilis
• Tuberculous ulceration
TREATMENT
GENERAL MEASURES
Appropriate health care
• Outpatient surgery with oral antibiotics (although in some cases, antibiotics may not be necessary) (4)[B]
• Inpatient surgery with IV antibiotics for supra-levator abscess or toxicity (3)[C]
Diet
Increase fiber and fluid intake.
Activity
Resume work and normal activity as soon as possible.
MEDICATION (DRUGS)
• Antibiotics
• Stool-softening laxatives
• Contraindications
- Refer to manufacturer's literature
• Precautions
- Refer to manufacturer's literature
• Significant possible interactions
- Refer to manufacturer's literature
SURGERY
• Perianal abscess
- Incise and drain abscess (4)[B]
- Local anesthetic frequently appropriate
- Pack wound with Iodoform gauze (24-48 hours).
• Ischiorectal abscess
- Incise and drain abscess (4)[B]
- General anesthetic usually required
- Pack wound with Iodoform gauze or similar packing (removed gradually over several days).
- Fistulectomy may be done at the same time in selected cases.
• Supralevator abscess
- Incise and drain abscess into lower rectum or anal canal (3)[C]
- General anesthesia required
• After surgery
- Sitz baths q2-4h
- Heating pad, heat lamp, or warm compress as needed for pain
- Encourage moving legs as soon as possible
- Prevent constipation.
FOLLOW-UP
PROGNOSIS
• Slow healing depending on extent of disease and concurrent illnesses, complete healing by 6 months if no complications
• Healing in infants may be complete in 1-3 weeks.
• Drainage alone results in cure rate of 50% or more.
COMPLICATIONS
• Possible anorectal fistula (in 25% of patients) (2,3)[C]
• Possible rectovaginal fistula
• Fecal incontinence due to rupture through sphincter muscle
• Recurrence of abscess if underlying cause not corrected
• Necrotizing infection with rapid progression, sepsis, and death (3)[C]
PATIENT MONITORING
Routine postoperative care with attention to wound healing, which should progress from the inside out
REFERENCES
1. Fazio VW. Anorectal disorders. In: Gastroenterology Clinics of North America. Philadelphia: Saunders; 1987.
2. Ziegler M, Azizkhan R, Weber T, et al., eds. Operative Pediatric Surgery. New York: McGraw-Hill, 2003
3. Townsend C, Beauchamp RD, Evers BM, et al. eds. Sabiston Textbook of Surgery, 17 ed. Philadelphia: Elsevier Saunders, 2006
4. Whiteford MH, Kilkenny J, Hyman N, et al. Practice parameters for the treatment of perianal abscess and fistula-in-ano (revised). Dis Colon Rectum 2005;48:1337-1342.

ANKYLOSING SPONDYLITIS

2008-12-31T01:37:00.000-08:00

ANKYLOSING SPONDYLITIS - Jane S. Kim, MD
BASICS
DESCRIPTION
Ankylosing spondylitis (AS) is a chronic inflammatory seronegative arthritis affecting the axial skeleton with primary involvement of the sacroiliac joint.
• System(s) Affected: Musculoskeletal
• Synonym(s): Rheumatoid spondylitis; Marie-Strumpell disease
EPIDEMIOLOGY
• Predominant age: Onset usually in early 20s, rarely occurs after age >40 years of age
• Predominant sex: Male > Female (3:1)
Incidence
• In white males: 0.5-5 per 1,000
• Less common in women and African Americans
Prevalence
0.1-0.2% in United States
RISK FACTORS
• HLA-B27 (1% of HLA-B27-positive adults likely to have AS)
• Positive family history
- 10% risk of developing AS for HLA-B27-positive child of spondylitic parent
Genetics
Familial clustering and higher than expected frequency of HLA-B27 tissue antigen
PATHOPHYSIOLOGY
Inflammation at the insertion of tendons causes new bone formation (enthesitis).
ETIOLOGY
Unknown
ASSOCIATED CONDITIONS
• Uveitis (25-30%)
• Iritis
• Psoriasis
• Aortic insufficiency (2%)

DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Insidious onset
• Duration >3 months
• Morning stiffness
• Frequently awaken at night to "walk off" stiffness
• Improvement in stiffness with activity
• Increased symptoms with rest
• Hip, shoulder, or knee complaints
• Constitutional symptoms (fatigue, weight loss, low-grade fever)
Physical Exam
• Subgluteal or low back pain and/or stiffness
• Pleuritic chest pain often an early feature
• Diminished range of motion in the lumbar spine in all three planes of motion
• Loss of lumbar lordosis
• Thoracocervical kyphosis (rarely occurs before 10 years of symptoms)
• Aortic regurgitation murmur (1%)
• Acute anterior uveitis
• Osteoporosis
• Plantar fasciitis
• Peripheral arthritis (20-30%)
TESTS
• Synovial fluid: Mild leukocytosis, decreased viscosity
• EKG: Conduction defects
• Measurement of respiratory excursion of chest wall: 5 cm maximal respiratory excursion of chest wall measured at fourth intercostal space
• 2.5 cm is virtually diagnostic of ankylosing spondylitis
• Wright-Schober test for lumbar spine flexion is abnormal or 5 cm.
- Mark the patient's back over the L5 spinous process and 10 cm above this point, then have the patient bend forward.The distance between the 2 marks should increase by 5 cm or more in normal persons.
Lab
• The HLA-B27 tissue antigen is present in 90% of White AS patients; there is a 5-8% incidence in the general population.
• ESR and CRP are elevated in the majority of the cases but correlate poorly with disease activity and prognosis. Mild elevation in serum IgA, creatine kinase, alkaline phosphatase, and complement may be seen.
• Absent rheumatoid factor
• Mild normochromic anemia (15%)
Imaging
• Sacroiliac joint early: Sclerosis on both sides of joint not extending >1 cm from articular surface = sacroiliitis
• Sacroiliac joint late
- Ankylosis of sacroiliac joint
- Osteopenia
• Spine
- "Squaring" of vertebral bodies and ossification of annulus fibrosis giving appearance of "bamboo spine"
- Ankylosis of facet joints
• Peripheral joint
- Symmetric erosive changes in larger joints
- Pericapsular ossification, sclerosis, loss of joint space
• Preferred position for imaging the SI joints with plain films is oblique projection. MRI of the SI joints may show increased signal from the bone and bone marrow suggesting osteitis and edema.
Diagnostic Procedures/Surgery
• Physical examination
• Radiographs: Sacroiliac joint films, lumbar spine series
• DEXA bone scan (high incidence of osteoporosis)
• MRI may show early enthesitis.
Pathological Findings
• Erosive changes coupled with new bone formation at the attachment of the tendons and ligaments to the bone resulting in ossification of periarticular soft tissues
• Synovial changes are indistinguishable from rheumatoid arthritis.
• Erosion of articular cartilage is less severe than in rheumatoid arthritis.
DIFFERENTIAL DIAGNOSIS
• Reactive arthritis
• Psoriatic arthritis
• Diffuse idiopathic skeletal hypertrophy (DISH)
• Spondylitis associated with inflammatory bowel disease
• Rheumatoid arthritis
TREATMENT
GENERAL MEASURES
• Appropriate healthcare: Outpatient
• Posture training and range of motion exercises for spine are essential.
• Firm bed
• Sleep in supine position without a pillow
• Breathing exercises 2-3  a day
• Smoking cessation
Activity
• Encourage active lifestyle. Swimming, tai chi, and walking are recommended.
• Avoid trauma/contact sports.
• Avoid prolonged standing.
SPECIAL THERAPY
Physical Therapy
Exercises to improve posture and flexibility
MEDICATION (DRUGS)
First Line
• NSAIDs provide symptomatic relief, usually rapidly.
- A dramatic response to NSAIDs can be diagnostic of AS.
• Selection is empiric, but traditionally indomethacin 50 mg t.i.d. or q.i.d. has been used.
• Intra-articular steroid injections may provide relief though systemic corticosteroids typically do not.
• Osteoporosis prophylaxis and treatment
• Injection of a long-acting corticosteroid into the sacroiliac joints may be beneficial in very symptomatic patients. Avoid systemic corticosteroids.
• Precautions
- All patients on long-term NSAIDs should have their renal function monitored.
- NSAIDs may aggravate peptic ulcer disease or cause gastritis.
- NSAIDs should be used with caution in patients with a bleeding diathesis or patients requiring anticoagulants.
- Refer to the manufacturer's profile of each drug for significant possible interactions.
Second Line
• Used when patients fail NSAIDs or become intolerant of them
• Sulfasalazine and methotrexate caused clinical improvement.
• Etanercept (anti-tumor necrosis factor alpha agent) showed rapid, significant, and sustained improvement and is now FDA-approved for AS. (2)[A]
• Infliximab can be efficacious and is also FDA-approved for AS. (4)[A]
• Thalidomide shows promise. (3)[C]
• Pamidronate may also help function and decrease disease activity. (3)[C]
SURGERY
• Total hip replacement should be considered to restore upright posture and to control pain in severe cases.
• Vertebral osteotomy can improve posture for those patients with severe cervical flexion.
FOLLOW-UP
DISPOSITION
Issues for Referral
Rheumatologists will be experienced in diagnosing and treating AS.
PROGNOSIS
• Unpredictable course
• Prognosis good if mobility and upright posture maintained
• Usually progressive disability
• No difference in overall mortality
COMPLICATIONS
• Spine
- Spinal fusion causing kyphosis
- Cervical spine fracture (high mortality rate)
- C1-C2 subluxation
- Cauda equina syndrome (rare)
• Peripheral joint ankylosis
• Pulmonary
- Restrictive lung disease
- Upper lobe fibrosis (rare)
• Cardiac
- Conduction defects
- Aortic insufficiency
- Aortitis
- Pericarditis
• Uveitis and cataracts
• Renal
- IgA nephropathy
- Amyloidosis (rare)
• Cutaneous LCV (rare)
• Gastrointestinal: Illeal and colonic mucosal ulcerations, mostly asymptomatic
PATIENT MONITORING
Visits every 6-12 months to monitor posture and range of motion
REFERENCES
1. Bennett DL, Ohashi K, El-Khoury GY. Spondyloarthropathies: Ankylosing spondylitis and psoriatic arthritis. Radiol Clin North Am. 2004;42(1):121-134.
2. Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med. 2002;346:1349-1356.
3. Davis JC Jr, Huang F, Maksymowych W. New therapies for ankylosing spondylitis: Etanercept, thalidomide, and pamidronate. Rheum Dis Clin North Am. 2003;29:481-494.
4. De Keyser F, Baeten D, Van den Bosch F, Kruithof E, Mielants H, Veys EM. Infliximab in patients who have spondyloarpthropathy: Clinical efficacy, safety, and biological immunomodulation. Rheum Dis Clin North Am. 2003;29(3):463-479.
5. Kataria RK, Brent LH. Spondyloarthropathies. Am Fam Phys. 2004;69(12):2853-2860.

ANKLE FRACTURES

2008-12-31T01:35:00.000-08:00

ANKLE FRACTURES - Heather C. Killie, MD
BASICS
DESCRIPTION
• Fractures involving the distal fibula (lateral malleolus) and/or distal tibia (medial malleolus and plafond)
• Includes a range of injuries to bones and ligaments of the ankle
GENERAL PREVENTION
• Proper shoe wear (i.e., flat, supportive shoes)
• Avoid running or walking on uneven or slick surfaces.
EPIDEMIOLOGY
• One of the most common fractures requiring orthopedic care
• Lateral malleolus more commonly involved (account for 2/3 of all ankle fractures)
Incidence
• Age-specific incidence increases in men >60 and women >50 years of age
• Highest incidence in elderly women (1)[B]
ALERT
Pediatric Considerations
• Pediatric will present with fractures involving the growth plates
• Most commonly a Salter-Harris I fracture of the distal fibula
RISK FACTORS
• Increased body mass index
• History of smoking
• No association between general health and risk for ankle fracture
PATHOPHYSIOLOGY
The location and pattern of injury depend on foot position and the direction of force applied. Most commonly the foot is plantarflexed and inverted, and the force is external rotation.
Axial load can cause a tibial plafond (a.k.a. pilon) fracture, which is an intra-articular fracture of the distal tibia where it articulates with the talus.
ETIOLOGY
Fall or twisting injury to the ankle
ASSOCIATED CONDITIONS
• Ankle sprains
• Syndesmosis injury
• Ankle or subtalar dislocation
• Fracture of the metatarsals, talus, calcaneus
• Osteochondral fracture (subchondral fracture of the distal tibia or talus)
• Neurovascular injury (very rare)

DIAGNOSIS
PRE HOSPITAL
• If ankle is obviously deformed, it should be reduced and provisionally splinted after adequate pain control is achieved.
• Place ice on ankle and elevate extremity
SIGNS AND SYMPTOMS
• Pain, swelling, and ecchymosis
• Pain or inability to bear weight
• Possible deformity
History
• Mechanism of injury
- Fall or twisting injury
• Timing of injury
• Past history of ankle injuries
• Any other injuries sustained
Physical Exam
• Inspect the ankle and foot for swelling and ecchymosis.
• Inspect the skin for tenting or lacerations.
• Palpate dorsalis pedis and posterior tibial pulses
• Palpate medial and lateral malleoli, proximal leg, and foot
• Sensory and motor exam of ankle and foot
• Rule out compartment syndrome (very rare), especially of the deep posterior compartment of the leg.
TESTS
Lab
Routine lab studies are not needed unless the fracture is operative.
Imaging
• Ottawa Ankle Rules help the clinician determine when to get x-rays. (2)[A]
• X-rays when patient has pain at either malleoli and 1 or more of following:
- Age >55
- Inability to bear weight
- Bony tenderness at posterior edge or tip of either malleoli
• 3 standard views: AP, Lateral, Mortise (15 internal rotation view)
• When foot pain present, get 3 views of foot
Diagnostic Procedures/Surgery
• Arthroscopy is an option in cases of persistent pain or suspicion of an OCD lesion.
• Open reduction, internal fixation in cases of instability (See "Treatment" section)
DIFFERENTIAL DIAGNOSIS
• Stress fracture
• Ankle sprain
• Osteochondral fracture
• Talus fracture
• 5th Metatarsal fracture
• Calcaneus fracture
TREATMENT
PRE-HOSPITAL
• If ankle is obviously deformed, it should be reduced with adequate pain control and provisionally splinted per first-aid protocol.
• Ice and elevate the extremity.
STABILIZATION
• As above if obvious deformity
• Place leg in a padded posterior splint to include toes to just below knee.
• If the fracture is open, remove any debris from the wound, place a moist dressing over the wound, and immediately contact an orthopedic surgeon.
• Obtain x-rays.
GENERAL MEASURES
Activity
• Non-weight bearing in all fractures
• EXCEPTION
- Isolated avulsion fractures of the tip of the lateral malleolus may be weight bearing as tolerated.
Nursing
• Apply ice.
• Instruct patient to keep leg elevated
• Control pain.
SPECIAL THERAPY
Physical Therapy
Early range of motion is key to prevent stiffness.
• Encourage toe and knee motion as soon as possible.
• Start ankle ROM as soon as there is evidence of fracture healing (usually 6 weeks).
MEDICATION (DRUGS)
• In general, ankle fractures are painful, particularly in the 1st 5-7 days following an injury. As the swelling decreases, so does the pain.
First Line
• Acetaminophen
• Opiod analgesics (i.e., hydrocodone)
• Avoid NSAIDs acutely (may delay healing of fractures)
Second Line
Non-opiod analgesics (i.e., tramadol)
SURGERY
• Absolute surgical indications
- Open fractures (fix within 6-8 hours)
• Relative surgical indications
- Gross instability (i.e., dislocation on presentation, bi- or tri-malleolar ankle fractures)
- Displacement after closed reduction attempt
- Displaced, comminuted distal tibia fractures
• Surgical options
- Open reduction internal fixation with plates and screws (most commonly)
- External fixation for comminuted distal tibia fractures
• Timing of surgery
- Within 6-8 hours if skin open
- After swelling decreased in all other cases (preferably not >1 week)
• Length of recovery
- In general, 6-8 weeks for healing
- 6-8 weeks in a cast or splint (longer if fracture involves both medial and lateral malleoli)
- 2-4 months for syndesmotic injury
- Orthopedist may allow range of motion after 4 weeks and place in removable cast boot (fracture pattern and surgeon dependent)
FOLLOW-UP
Most ankle fractures require close follow-up by an orthopedic surgeon (see "Referral" section)
DISPOSITION
• Patient should be transferred to the emergency department if
- Open fractures
- Dislocated ankle
- Neurovascular injury
- Possible compartment syndrome
• Otherwise, patient should be referred to an orthopedic surgeon
Admission Criteria
Admit to the hospital if
Open fracture
Neurovascular injury
Cannot maintain non-weight bearing status and requires physical therapy consultation
Concern of skin compromise
Concern of mechanism of injury (i.e., syncope, MI, head injury)
Discharge Criteria
When patient has completed the following
Able to ambulate with walker/crutches
Medical work-up (if needed) is completed
Appropriate orthopedic follow-up is arranged
Elderly patients may require a short stay in a rehabilitation facility.
Issues for Referral
• Most ankle fractures should be seen by an orthopedic surgeon within 5-7 days, earlier if a reduction is needed.
• Open fractures should be seen by an orthopedic surgeon immediately.
PROGNOSIS
• Good results can be achieved in most ankle fractures without surgery, provided the ankle mortise is maintained. (3)[B]
• Long term, some patients may develop ankle arthritis; timing is unpredictable.
• Effusion or pain can persist for up to 1 year.
COMPLICATIONS
• Non-operative
- Displacement of the fracture
- Malunion
- Skin breakdown
- DVT (rarely pulmonary embolism)
• Operative
- Infection
- Loss of fixation
- Nonunion or malunion
- Skin breakdown
- DVT (rarely pulmonary embolism)
PATIENT MONITORING
• Serial x-rays should be performed weekly for 4 weeks if there is any question about stability.
• Otherwise, x-rays should be performed at 2 weeks, 4 weeks, and 8 weeks or until the fracture is healed.
REFERENCES
1. Court-Brown CM, McBirnie J, Wilson G. Adult ankle fracturesan increasing problem? Acta Orthop Scand. 1998;69(1):43-47.
2. Stiell IG, Greenberg GH, McKnight RD, et, al. Decision rules for the use of radiography in acute ankle injuries: Refinement and prospective validation. JAMA. Mar 1993;269:1127-1132.
3. Michelson JD. Ankle fractures resulting from rotational injuries. J Am Acad Orthop Surg. 2003;11:403-412.

ANIMAL BITES

2008-12-31T01:33:00.000-08:00

ANIMAL BITES - George R. Bergus, MD
BASICS
DESCRIPTION
• Bite wounds to humans from dogs, cats, other animals including humans
• System(s) Affected: Endocrine/Metabolic; Hemic/Lymphatic/Immunologic; Nervous; Skin/Exocrine
ALERT
Geriatric Considerations
• Serious injury from any bite wound is more common >50 years old, those with wounds in the upper extremities, or those with puncture wounds.
• Increased risk of infection >50 years old
Pediatric Considerations
Young children are more likely to have severe bites.
GENERAL PREVENTION
• Instruct children and adults about animal hazards.
• Educate dog owners about responsible dog ownership.
• Strongly enforce animal control laws.
EPIDEMIOLOGY
Incidence
• Dog bites: 1,200/100,000
• Cat bites: 160/100,000
• Snake bites: 15/100,000 nonvenomous bites and 3/100,000 venomous bites per year
• Lifetime prevalence for animal bite: 50,000/100,000
• Dog bites are responsible for 1/3 million emergency room visits per year
Prevalence
• Predominant age: All ages, but children more likely to be affected
• Predominant sex: Male > Female
RISK FACTORS
• Dog bites are more common during warm weather.
• Male dogs are more likely to bite.
• Clenched-fist injuries are frequently associated with the use of alcohol.
ETIOLOGY
• Most bite wounds are from a domestic pet known to the victim.
• Large dogs are the most common source of bite wounds.
• Human bites are often the result of one person striking another in the mouth with a clenched fist.

DIAGNOSIS
SIGNS AND SYMPTOMS
• Bite wounds can be tears, punctures, scratches, avulsions, or crush injuries.
• Dog bites (80-90% of bites)
- In adults, hands are most commonly affected.
- In children, the face is the most common site of injury, and involvement of the trunk is uncommon.
• Cat bites (10% of bites)
- Predominantly involve the hands, followed by lower extremities, face, and trunk
- Are more likely to become infected because of puncture nature of wounds
TESTS
Lab
• 85% of bite wounds will yield a positive culture, but culturing at time of injury is of little benefit
• Wound culture is essential in directing therapy.
- Some pathogens are slow growing, so cultures should be kept for 7-10 days
- Gram stain is sensitive but not specific for infecting organism
• Dog bites
- Pasteurella species is present in 50% of bites.
- Also found: Streptococcus viridans, Staphylococcus aureus, coagulase-negative Staphylococcus, Bacteroides, Capnocytophaga canimorsus, Fusobacterium
• Cat bites
- Pasteurella species is present in 75% of bites.
- The wound is often contaminated by other mixed bacteria, including several species of both aerobic and anaerobic organisms.
• Human bites
- Streptococcus species, Staphylococcus aureus, Eikenella corrodens, and various anaerobic bacteria are very common.
• Other animal bites
- Scant information on pathogens
• Drugs that may alter lab results
- Previous antibiotic therapy
Imaging
• If bite wound is near a bone or joint, a plain radiograph is needed to check for bone injury and to use for comparison later if osteomyelitis is suspected.
• In human bite wounds from clenched-fist injuries, order plain-film radiographs to check for metacarpal or phalanx fracture.
Diagnostic Procedures/Surgery
• Consider rabies prophylaxis for bats, nondomestic dogs; rarely skunks, foxes and raccoon
• Surgical exploration may be needed to ascertain extent of injuries.
• Exploration should be performed on all serious hand wounds, especially clenched-fist injuries involving a joint.
DIFFERENTIAL DIAGNOSIS
Diagnosis is straightforward; what is of concern is judging the risk to the patient from the injury and resulting infection.
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient, unless patient has fulminant infection requiring systemic antibiotics, close observation, or surgery
• Elevation of the injured extremity to prevent swelling
• Contact the local health department and consult about the prevalence of rabies in the species of animal involved.
MEDICATION (DRUGS)
First Line
• Consider antirabies therapy.
• Use tetanus toxoid in those previously immunized, but >5 years since their last dose.
• Consider tetanus immune globulin (TIG) in patients without a full primary series of immunizations.
• Prophylactic therapy if wound seen in 1st 12 hours
- Dog, cat, or animal: Amoxicillin-clavulanate 500-875 mg b.i.d. PO (pediatric: 20-40 mg/kg/d PO given t.i.d.)
- Snake bite: If venomous, the patient needs rapid transport to a facility capable of definitive evaluation. If an envenomation has occurred, the patient will need to receive antivenin unless envenomation was only minimal. Be sure patient is stable for transport; consider measuring and or treating coagulation and renal status along with any anaphylactic reactions before transport.
- Human bites: Amoxicillin-clavulanate (Augmentin) potassium, adult: 500 mg PO t.i.d. (pediatric: 20-40 mg/kg/d PO given t.i.d.)
• Established infection
- After patient has developed a clinical infection, amoxicillin-clavulanate potassium (Augmentin) can be used pending culture reports
• Contraindications: Do not use penicillin-derived antibiotics in those with penicillin allergy.
• Precautions: Prescribe dosage of antibiotics by body weight and renal function.
• Significant possible interactions: Antibiotics may decrease efficacy of oral contraceptives
Second Line
• Alternative therapy for penicillin-allergic patients (for prophylaxis or empiric treatment)
- ~10% cross-reactivity with cephalosporins in penicillin-allergic patients
- Dog bite: Moxifloxacin 400 mg/day  7 days in adults (pediatric: trimethoprim- sulfamethoxazole along with Clindamycin); avoid cephalexin due to resistant strains of Pasteurella multocida
- Cat bite: As for dog bite
- Human bite: Moxifloxacin 400 mg/day
• If hospitalized with established infection: Ampicillin-sulbactam (Unasyn) 1-2 g IV q6h or ticarcillin-clavulanate (Timentin) 3.1 g IV q4-6h
SURGERY
• Copious irrigation of the wound with normal saline via a catheter tip is needed to reduce risk of infection.
• Devitalized tissue needs debridement.
• Debridement of puncture wounds not advised.
• Consider surgical closure if the wound is clean after irrigation and bite is 12 hours old. Puncture wounds should be left open.
• Delayed primary closure in 3-5 days is an option for infected wounds.
• Splint hand if it is injured.
• Human bite wounds on the hands should not be primarily closed because of the high risk of infection. Large, gaping wounds should be reapproximated with widely spaced sutures or Steri-Strips.
FOLLOW-UP
PROGNOSIS
Wounds should steadily improve and close over by 7-10 days.
COMPLICATIONS
• Septic arthritis
• Osteomyelitis
• Extensive soft tissue injuries with scarring
• Sepsis
• Hemorrhage
• Death
• Gas gangrene can take an exceedingly rapid course and should be treated very aggressively.
PATIENT MONITORING
• Patient should be re-checked in 24-48 hours if not infected at time of 1st encounter
• Daily follow-up is warranted with active infections.
• If antibiotics are used for an active infection, the duration of therapy should be 7-14 days, depending on the severity of the infection and the clinical response.
REFERENCES
1. Stevens DL, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. 2005;41(10):1373-1406.
2. Fleisher GR. The management of bite wounds. N Engl J Med. 1999:340:138-140.
3. Griego RD, et al. Dog, cat and human bites: A review. J Am Acad Dermatol. 1995;33: 1019-1029.
4. Presutti RJ. Prevention and treatment of dog bites. Am Fam Physician. 2001;63(8):1567-1572, 1573-1574.
5. Sacks JJ, et al. Fatal dog attacks 1989-1994. Pediatrics. 1996;97:891-895.
MISCELLANEOUS
Rabies
• Contact your local health department for information about the risk of rabies.
• Most human rabies are related to bat bites. See also: Bartonella Infections; Cellulitis; Rabies; Snake Envenomations; Crotalidae; Elapidae

ANGIOEDEMA

2008-12-31T01:31:00.000-08:00

ANGIOEDEMA - Anatoli Freiman, MD
BASICS
DESCRIPTION
• Dermal (subcutaneous or submucosal) extravasation of fluid, leading to localized edema
• The release of inflammatory vasoactive mediators increases vascular permeability.
• The skin, gastrointestinal tract, and respiratory tract are most commonly involved. It is life threatening if the upper airway is affected. It usually resolves in hours to days.
• Can be idiopathic or induced by medications, allergens (e.g., food), or physical agents (e.g., vibration, cold)
• 2 rare but well-described categories of angioedema result from deficiency of C1 esterase inhibitor (C1 INH) of the compliment and kallikrein-kinin systems: Hereditary angioedema (HAE) and acquired angioedema (AAE).
- HAE type I (80-85%): Due to hereditary deficiency of C1-INH; recurrent episodes of angioedema, involving both skin and mucous membranes or intestinal mucosa (25% mortality)
- HAE type II (15-20%): Normal or elevated quantities of functionally impaired C1-INH
- HAE type III: Rare, recently described estrogen-dependent form
- AAE type I: Increased destruction of C1-INH, which occurs in patients with rheumatologic disorders and B-cell lymphoproliferative malignancies, such as leukemia, T-cell lymphoma, multiple myeloma, and essential cryoglobulinemia
- AAE type I is also reported with carcinomas, infections, and vasculitides. Immune complexes continuously activate C1, leading to consumption of C1-INH and precipitating angioedema.
- AAE type II: B cells secrete autoantibodies against C1-INH, leading to its inactivation
• Medication-induced angioedema
- Immunologic hypersensitivity, as in penicillin reaction
- Nonimmunologic, as in reactions to NSAIDs (e.g., aspirin)
- Angiotensin converting enzyme (ACE) inhibitors decrease levels of angiotensin II and stimulate production of bradykinin, a potent vasodilator, thus leading to angioedema. This may occur immediately or months after starting the drug.
• System(s) Affected: Skin/Exocrine
• Synonym(s): Angioneurotic edema; Quincke edema
GENERAL PREVENTION
• If etiology known, avoidance
• Avoid ACE inhibitors in patients with a history of angioedema.
EPIDEMIOLOGY
• Predominant age
- HAE: Infancy to second decade of life
- AAE: Typically patients > 40 years old.
• Predominant sex: Male = Female (idiopathic)
Incidence
• 1 in 5,000
• Accompanies urticaria 40-50% of time
RISK FACTORS
• Medications and foods that can cause allergic reactions
• ACE inhibitors are contraindicated in patients with C1-INH deficiency
Genetics
HAE types I and II are inherited in autosomal dominant mode, whereas type III is X-linked. HAE occurs in 25% of the patients as a result of spontaneous mutations.
PATHOPHYSIOLOGY
Similar pathophysiology for urticaria and angioedema: Localized anaphylaxis causes vasodilatation and vascular permeability of superficial (urticaria) or subcutaneous/deeper dermal tissue (angioedema)
ETIOLOGY
• Idiopathic
• Medication-induced: ACE inhibitors, NSAIDs, antibiotics, or estrogen contraceptives
- ACE inhibitors (ACEI) are ascribed to 10-25% of angioedema cases and mostly occur within the 1st 3-4 weeks of use. However, the 1st onset may be delayed years. Failure to react to re-challenge with drug does not rule out a cause-effect relationship between the ACEI and angioedema.
- Losartan (Cozaar), valsartan (Diovan), and irbesartan (Avapro), which are all angiotensin receptor blockers (ARB), can also cause angioedema. It can occur within 24 hours to 16 months after initiating losartan therapy.
• Allergen-induced: Food allergens, such as fish, nuts, and preservatives
• Physically induced: Cold, pressure, vibration
• Hereditary or acquired C1-INH deficiency
• Thyroid autoimmunity has been reported to be associated with angioedema.
ASSOCIATED CONDITIONS
• Urticaria
• Anaphylaxis

DIAGNOSIS
SIGNS AND SYMPTOMS
• Occurs alone or in association with urticaria in 50% of cases
• Angioedema usually does not cause itching in comparison to urticaria, but can cause burning.
• Relatively rapid onset of presentation; usually resolves spontaneously in 72 hours
• Skin
- Localized swelling; may occur anywhere on body; usually face, extremities, or genitalia; often asymmetric
- Frequently disfiguring and frightening to the patient
• Gastrointestinal
- May present with intermittent unexplained abdominal pain
• Respiratory
- May be associated with generalized anaphylactic reaction, potentially fatal if upper airway is compromised
History
• Acute onset of asymmetric localized swelling
• GI tract involvement may manifest as intermittent unexplained abdominal pain.
• In comparison to urticaria, angioedema is typically nonpruritic, but can cause burning.
Physical Exam
Subcutaneous swelling, usually of the face (eyelids, lips, ears, nose), and less often of the extremities or genitalia
TESTS
Lab
• If angioedema with urticaria and/or anaphylaxis, no testing is needed, but history should be directed to exposures: Foods, medications, exposures, etc.
• Without clear etiology and recurrence in angioedema and urticaria, CBC and ESR; macrocytosis implies a pernicious anemia; eosinophilia my imply atopy or rarely parasitic infection. Elevated ESR may imply systemic disorders.
• In recurrent angioedema without clear etiology and without urticaria, consider ordering C4. Low serum C4 is a very sensitive, but nonspecific, screening test for hereditary and acquired C1-INH deficiency. If C4 is normal, urticaria work-up is recommended.
• If C4 is low, C1-INH assay (immunoreactive) is performed for HAE type I and C1-INH assay (functional) for HAE type II.
• C1q is decreased in acquired C1-INH deficiency.
• If C4 and C1q are low (as in AAE), neoplastic and autoimmune work-up are warranted. Routine blood tests, a smear, protein electrophoresis, immunophenotyping of lymphocytes, and imaging studies are often undertaken to rule out hematological malignancies or cancer.
• May alter lab results
- Antihistamines
- H2-blockers
- Tricyclic antidepressants
Imaging
As part of neoplastic work-up if relevant
Diagnostic Procedures/Surgery
Skin biopsy (may be nonspecific)
Pathological Findings
Edema of deep dermis and subcutaneous tissue. Variable perivascular and interstitial infiltrate
DIFFERENTIAL DIAGNOSIS
• Urticaria
• Allergic contact dermatitis
• Connective tissue disease: Lupus, dermatomyositis
• Anaphylaxis
• Cellulitis, erysipelas
• Lymphedema
• Diffuse subcutaneous infiltrative process
TREATMENT
PRE-HOSPITAL
• Ensure airway patency 1st! Protect the airway if the mouth, tongue, and/or throat are involved.
• Perform CPR and transport to an emergency facility, if necessary.
STABILIZATION
If anaphylaxis (circulatory collapse or airway compromise), consider epinephrine (1:1000) SC 0.3-0.5 q15min.
GENERAL MEASURES
• Symptomatic, supportive management
• Avoid known triggers.
• Cool, moist compresses to control itching or burning
MEDICATION (DRUGS)
First Line
• 1st generation antihistamines for acute angioedema
- Older children and adults: hydroxyzine (Vistaril 5 mg/5 cc, 25 tablets) 10-25 mg t.i.d. or diphenhydramine (Benadryl) 25-50 mg q6h
- Children under 6 years of age: Diphenhydramine 12.5 mg (elixir) q6-8h (5 mg/kg/day)
• 2nd generation H1 blockers are less sedating because they do not cross the blood-brain barrier.
- Fexofenadine (Allegra) 60 mg b.i.d.
- Loratadine (Claritin) 10 mg daily
- Acrivastine (Semprex) 8 mg t.i.d.
- Cetirizine (Zyrtec) 10 mg daily, which is more sedating than others in this class
• Anaphylaxis
- Intubation if airway is threatened
- Epinephrine 1:1,000, 0.2-0.3 mL IV or SQ
- Specific HAE and AAE therapy
- C1-INH concentrate
- Attenuated androgens: Danazol or stanozolol are particularly effective for prevention of HAE because they increase the amount of active C1-INH. Give 200-600 mg daily for 1 month, then 5 days on, 5 days off. The side effects are headaches, weight gain, and hematuria.
- Antifibrinolytic agents (plasmin inhibitors), such as tranexamic acid and aminocaproic acid, may also be used, but are not as effective as attenuated androgens in the management of HAE. On rare occasions they can cause thrombophlebitis, embolism, or myositis.
• Contraindications
- Danazol not to be used in childhood, pregnancy, lactation, and prostate cancer
• Precautions
- Drowsiness with 1st generation drugs
- Second generation H1 blockers should be used with caution in pregnancy and the elderly.
Second Line
Doxepin (Sinequan) may be effective for angioedema (10-25 mg at bedtime)
FOLLOW-UP
PROGNOSIS
Most patients with idiopathic angioedema do well. Chronic forms depend on underlying pathology.
COMPLICATIONS
• Anaphylaxis
• Respiratory compromise
PATIENT MONITORING
• Diagnostic work-up if symptoms are severe, persistent, or recurrent
• Protect airway if mouth, tongue, or throat is involved
REFERENCES
1. Bowen T, et al. Canadian 2003 international consensus algorithm for the diagnosis, therapy, and management of hereditary angioedema. J Allergy Clin Immunol. 2004;114(3):629-637.
2. Charlesworth EN. Differential diagnosis of angioedema. Allergy Asthma Proc. 2002;23:337-339.
3. Frigas E, Nzeako UC. Angioedema. Clin Rev Allerg Immunol. 2002;23:217-231.
4. Heymann WR. Acquired angioedema. J Am Acad Dermatol. 1997;26:611-615.
5. Kim JS, Pongracic JA. Hereditary and aquired angioedema. Allergy Asthma Proc. 2004;25:S47-S49.
6. Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema: a broad review for clinicians. Arch Intern Med. 2001;161:2417-2429.

ANGINA

2008-12-31T01:30:00.000-08:00

ANGINA - Philip P. Lobstein, MD
BASICS
DESCRIPTION
• Symptom complex resulting from mismatch of myocardial oxygen demand and supply:
- Classic angina: A sense of choking or of pressure or heaviness deep to the precordium, usually brought on by exertion or anxiety and relieved by rest
- Anginal equivalent: Exertional dyspnea or exertional fatigue, which results from myocardial ischemia and is relieved by rest or nitroglycerin
- Variant angina: Also referred to as Prinzmetal angina; describes angina occurring at rest in atypical patterns such as after exercise or nocturnally. Prinzmetal angina is caused by coronary artery spasm, and is associated with ECG changes (usually ST elevation) during symptoms
- Stable angina: Predictable chest discomfort that occurs in a consistent pattern at a certain level of exertion and is relieved with rest or nitroglycerin
- Unstable angina: Pain that is new or is changed in character to become more frequent, more severe, or both. Unstable angina portends myocardial infarction in a certain percentage of patients.
• System(s) Affected: Cardiovascular
• Synonym(s): Heberden syndrome
ALERT
Geriatric Considerations
Patients may be very sensitive to the side effects of the medications.
Pediatric Considerations
Suspect familial dyslipidemias in children presenting with manifestations of coronary artery disease.
Pregnancy Considerations
Other diagnoses should be excluded, and the patient managed closely by an obstetrician or family physician and cardiologist: The metabolic demands of pregnancy will exacerbate symptoms and directly interfere with treatment.
GENERAL PREVENTION
• Discontinue tobacco, adherence to low fat/low cholesterol diet, regular aerobic exercise program
• Antilipidemics if indicated by current ATP guidelines
• Daily aspirin in those without contraindications
EPIDEMIOLOGY
• Predominant age: Most common in middle age and older men; postmenopausal women
• Predominant sex: Male > Female (before menopause)
Incidence
Presenting symptom of coronary artery
• Male: 38%
• Female: 61%
RISK FACTORS
• Family history of premature coronary artery disease (CAD)
• Hypercholesterolemia
• Hypertension
• Tobacco abuse
• Diabetes mellitus
• Male gender
• Advanced age
• Morbid obesity
• Hyperhomocysteinemia (possibly)
Genetics
Coronary artery disease has genetic implications.
ETIOLOGY
• Atherosclerosis of the coronary arteries
• Coronary artery spasm
• Aortic stenosis
• Hypertrophic cardiomyopathy
• Severe hypertension
• Aortic insufficiency
• Primary pulmonary hypertension
ASSOCIATED CONDITIONS
• Hypercholesterolemia
• Claudication, Peripheral vascular disease
• Arterial aneurysms
• Mitral regurgitation
• Papillary muscle dysfunction
• Ventricular aneurysm
• Abdominal aortic aneurysm
• Hypertrophic subaortic stenosis
• Primary hyperthyroidism
• Pernicious anemia and other high output states

DIAGNOSIS
SIGNS AND SYMPTOMS
• Precordial pressure or heaviness, radiating to the back, neck, or arms; brought on by exertion, emotional stress, meals, cold air, or smoking; and relieved by rest or nitrates
• Discomfort may radiate to the neck, lower jaw, teeth, shoulders, and inner aspects of the arms or back.
• Discomfort may be described with a clenched fist over the sternum (Levine sign).
• Dyspnea on exertion may present as the only symptom.
• A choking sensation on exertion is a classic symptom.
• Atypical symptoms are more likely in women, elderly, and diabetic patients.
History
• Quality of any previous anginal episodes and pattern over time
• Underlying history of heart disease or valvular disease
• Family history of MI, CAD, sudden death
Physical Exam
May see signs of dyslipidemia (xanthomas, xanthelasma, diminished peripheral pulses, carotid bruits).
TESTS
• ECG
- May show evidence of ischemia or prior myocardial infarction; follow-up testing via angiography is warranted. Other findings are nonspecific and tracings are frequently normal.
- Bundle branch block, Wolff-Parkinson-White syndrome, or intraventricular conduction delay may make the ECG unreliable.
• If normal ECG, exercise stress treadmill testing (ETT) based on probability is indicated.
- ETT with imaging-via echocardiography or perfusion imaging with sestamibi.
- In patients who cannot tolerate exercise, pharmacologic stress testing should be performed
- Women have lower sensitivity and specificity with ETT than do men; exercise echocardiography is indicated
- In Men
 Low probability: ETT without imaging
 Intermediate probability: ETT with imaging
 High probability: ETT prior to angiography
Lab
• Total cholesterol: Frequently elevated
• HDL cholesterol: Frequently reduced
• LDL cholesterol: Frequently elevated
• CRP: Only useful (and offers no better predictive value than standard CHD risk factors) in those with Intermediate to high risk; should be measured at least twice over 2 weeks; is not predictive in low risk patients and in those on a -blocker or statin.
Imaging
• Radionuclide scintigraphy
• Stress echocardiography
• Stress scintigraphy
• Coronary angiography
Diagnostic Procedures/Surgery
• Definitive evaluation requires coronary arteriography for confirmation and delineation of coronary disease, and direction of interventional therapy or surgery. Coronary artery stenting has proven very effective, with restenosis rates (in skilled hands) often 10%, eliminating need for surgery in many cases.
• Surgery in CAD not amenable to angioplasty, and stenting has proven to have a long-term benefit.
Pathological Findings
Atherosclerosis of the coronary arteries
DIFFERENTIAL DIAGNOSIS
• Esophagitis (GERD)
• Esophageal spasm
• Peptic ulcer disease
• Gastritis or nonulcer dyspepsia
• Cholecystitis
• Costochondritis
• Pericarditis
• Aortic dissection
• Pleurisy
• Pulmonary embolus
• Pulmonary hypertension
• Pneumothorax
• Radiculopathy
• Shoulder arthropathy
• Psychological: Anxiety and panic disorders
TREATMENT
PRE-HOSPITAL
• EMS activation if chest discomfort unimproved or worsening 5 minutes after 1 nitroglycerin dose (1)[C]
- EMS to initiate IV, O2, and monitor
- Aspirin administration if ACS suspected and not previously taken or contraindicated
GENERAL MEASURES
• The patient's symptoms should be brought under control medically. If symptoms are unstable, hospitalization is warranted.
• Treatment goal involves reducing myocardial oxygen demand or to increase oxygen supply.
• Noninvasive testing often is indicated as a means of stratifying the patient's risk for an event that might seriously compromise myocardial function.
• Quit smoking.
• Minimize emotional stress.
• Weight reduction in obese patients (2)[C]
Diet
Low-fat, low-cholesterol, low-salt diet
Activity
• As tolerated after consulting physician
• Exercise program after physician's approval; very effective if consistent
SPECIAL THERAPY
Complementary and Alternative Medicine
Relaxation/stress reduction therapy may help reduce anginal aggravations.
MEDICATION (DRUGS)
First Line
• Aspirin: 81-325 mg/d
• -Blockers are effective in reducing heart rate and thereby decreasing oxygen consumption and reducing angina
- Atenolol 25-100 mg/d, metoprolol 25-100 mg b.i.d., or bisoprolol 2.5-10/d
- Adjust doses according to clinical response. Aim to maintain resting heart rate of 50-60 beats per minute.
- Side effects are infrequent but include fatigue, exercise intolerance, erectile dysfunction, and exacerbation of peripheral vascular and obstructive pulmonary disease.
• Nitroglycerin 0.4 mg SL is the most effective therapy for acute anginal episodes
- May repeat 2-3 times over a 10-15 minute period; if no relief, the patient should seek immediate medical attention.
• Long-acting nitrates (mononitrates or transdermal nitrates)
- Should be used with a drug-free interval of 10-14 hours to prevent tolerance
- Tachyphylaxis occurs rapidly.
- Preload reduction and coronary vasodilatation
- Side effects: Headaches and hypotension, tend to clear with continued usage.
- A -blocker or calcium channel blocker should be used in conjunction with the nitrates during the drug-free interval.
- Caution patients not to use in conjunction with oral medicine for erectile dysfunction, such as sildenafil (Viagra).
• Long-acting calcium channel blockers: Verapamil 160-480 mg/d or diltiazem 90-360 mg/d, or nifedipine 30-120 mg/d, or amlodipine 5-20 mg/d. Drug of choice for variant angina. The various agents have their own individual side effects (i.e., verapamil, constipation; nifedipine, peripheral edema).
• HMG CoA reductase inhibitors (e.g., atorvastatin, pravastatin, lovastatin) for hypercholesterolemia: These drugs decrease incidence of symptomatic CAD and reduce both myocardial infarction and death from MI. LDL target levels below 100 mg/dL in diabetes mellitus and 130 mg/dL in low- to moderate-risk patients.
• ACE inhibitors (ramipril 10 mg) in patients with CAD or other vascular disease (3)[B], and particularly those with diabetes or left ventricular (LV) systolic dysfunction (3)[A] have been shown to reduce both cardiovascular death and MI.
• Heparin: Low-molecular-weight heparin should be initiated in patients hospitalized with unstable angina.
• Glycoprotein IIb/IIIa receptor antagonists (Integrilin): Indicated in certain patients hospitalized with unstable angina
• Combination therapy may be used (especially nitrates plus calcium antagonists with or without -blockers).
• Contraindications:
- Sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) with nitrates should be avoided due to the risk of hypotension and possible death.
• Precautions: Avoid verapamil and diltiazem with compromised ventricular function (LV ejection fraction 40%) especially in conjunction with -blockers.
• Significant possible interactions:
- Combination therapies may impair LV function and precipitate heart failure.
- -Blockers and calcium channel blocker: May combine to produce symptomatic heart block, although either class of drug may act alone in producing this side effect
- Niacin may worsen glucose intolerance.
Second Line
• Current ATP guidelines support the use of lipid-lowering drugs in patients with unfavorable lipid profiles and suspected or documented CAD with or without symptoms (4)[A].
• Consider adding clopidogrel (Plavix) to ASA for severe diffuse CAD. The use of Plavix is indicated after stent placement for at least 9 months to significantly reduce restenosis rates.
SURGERY
Coronary artery bypass graft surgery, angioplasty, stent placement, atherectomy in selected cases
FOLLOW-UP
DISPOSITION
Admission Criteria
Unstable symptoms warrant hospitalization for evaluation.
PROGNOSIS
• Variable; depends on the extent of CAD as well as LV function
• Annual mortality is 3-4% overall
COMPLICATIONS
• Related to myocardial damage occurring during infarction
• Arrhythmia
• Cardiac arrest
• Congestive heart failure
PATIENT MONITORING
• Depends on the frequency and severity of the complaints
• Hospitalization is indicated in patients diagnosed with unstable angina.
REFERENCES
1. Antman EM, Ane DT, Armstrong PW, et al. Guidelines for the management of patients with ST-elevation myocardial infarctionexecutive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2004;110:588-636.
2. Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable anginasummary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2003;107:149-158.
3. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor ramipril on cardiovascular events in high-risk patients. The HOPE Study Investigators. N Engl J Med. 2000;342:145-153.
4. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

ANEURYSM OF THE ABDOMINAL AORTA

2008-12-31T01:27:00.000-08:00

ANEURYSM OF THE ABDOMINAL AORTA - David H. Stubbs, MD
BASICS
DESCRIPTION
A permanent localized (i.e., focal) dilatation of the abdominal aorta having at least a 50% increase in diameter compared to the expected diameter of the artery. The clinical presentation of aneurysms relates to location, size, type, and comorbid factors affecting the patient. The majority of aneurysms are asymptomatic. Some present with rupture, others with embolism or thrombosis. The management and indications for surgical repair is dictated by the natural history of the aneurysm, the type, the consequences of repair, and the general status of the patient. There are two types, which are infrarenal (90%) and thoracoabdominal.
• System(s) Affected: Cardiovascular; Hemic/ Lymphatic/Immunologic
• Synonym(s): Aortic aneurysms; AAA
ALERT
Geriatric Considerations
Familial aggregations exist, but pathogenesis relates to interaction of genetic, environmental, and biochemical factors.
- Marfan syndrome
- Ehlers-Danlos syndrome
Pediatric Considerations
Etiology more likely infectious or collagen disorders
GENERAL PREVENTION
Screening: 1-time ultrasound screening for AAA in male patients, ages 65-75 who have ever smoked >100 cigarettes
EPIDEMIOLOGY
• Predominant age: Elderly
• Predominant sex: Male > Female (4:1)
Incidence
• >15,000 deaths per year
• 10th leading cause of death in males >55
- In men >60 years: 2-5%
- In men >65 years: 6%
- In men >75 years: 11%
• In women >65 years: 4%
• High risk groups
- Coronary disease: 5-9%
- Peripheral vascular disease: 10-15%
- 1st degree relative with AAA: 25%
- Males = 40% risk
- Females = 15% risk
- Obese patients >65 years
- Presence of peripheral aneurysms
RISK FACTORS
• Hypertension
• Nicotine
• COPD
• Familial: Siblings of patients with AAA
ETIOLOGY
• Atherosclerosis
• Inflammatory (5-10%)
• Traumatic
• Genetic predisposition (Marfan, Ehlers-Danlos)
ASSOCIATED CONDITIONS
• Marfan syndrome
• Ehlers-Danlos syndrome

DIAGNOSIS
SIGNS AND SYMPTOMS
Physical Exam
Majority of patients with abdominal aortic aneurysm (AAA) are asymptomatic. Many are discovered during radiologic procedures performed for other reasons.
• Pulsatile epigastric mass
• Vague abdominal pain
- May radiate to the back of flank
• Encroachment by aneurysm
- Vertebral body erosion
- Gastric outlet obstruction
- Ureteral obstruction
• Lower extremity ischemia secondary to microembolization or macroembolization of mural thrombus
• The triad of shock, pulsatile mass, and abdominal pain should always suggest rupture of AAA
- Shock may be absent if the rupture is contained.
- Palpable pulsatile mass may be absent in up to 50% of the patients with rupture.
- Pain may radiate to the back or into the groin.
- Rupture associated with 90% mortality rate.
• Unusual presentations
- Primary aortoenteric fistula: Erosion/rupture of AAA into duodenum
- Aortocaval fistula: Erosion/rupture of AAA into vena cava or left renal vein
- Inflammatory aneurysm: Encasement of aneurysm by thick inflammatory rind associated with chronic abdominal pain, weight loss, and elevated ESR
- Surrounding viscera are densely adherent.
ALERT
Geriatric Considerations
More common in this age group and may present atypically
TESTS
Lab
Evaluation for concomitant CAD
• Selective evaluation for CAD is appropriate prior to elective AAA repair (i.e., cardiac clearance).
• Patients with mild, stable cardiac symptoms should have a noninvasive cardiac stress study.
• Coronary revascularization should be performed when the CAD would merit intervention on its own.
Imaging
Screening: 1-time ultrasound screening for AAA in male patients, ages 65-75, who have ever smoked >100 cigarettes
Diagnostic Procedures/Surgery
• Clinical examination
• Ultrasonography is the preferred initial diagnostic tool in suspected AAA, but is not reliable for a diagnosis of a rupture.
• CT scans are the preferred preoperative study. Avoid contrast if the patient has significant renal insufficiency. CT scans assist in the diagnosis of an inflammatory aneurysm.
• MRI: Similar to CT and avoids contrast. MR angiography may replace arteriograms.
• Aortography: Does not define outside dimensions of aneurysms.
• Indications for aortography
- Associated renovascular hypertension
- Symptoms of visceral angina
- Significant iliofemoral occlusive disease
- Peripheral aneurysms
- Horseshoe or pelvic kidney
- Prior colectomy
DIFFERENTIAL DIAGNOSIS
• Abdominal masses transmitting aortic pulse
• Other causes of abdominal pain (e.g., peptic ulcer disease)
• Other causes of back pain (e.g., arthritis, metastatic disease)
TREATMENT
STABILIZATION
• The treatment of AAA is elective repair.
• The prevention of AAA is elective repair.
GENERAL MEASURES
• Control hypertension
• Treat atherosclerotic risk factors
• Stop smoking
SURGERY
• Repair when
- Rupture occurs
- Size >5.5 cm (or >6 cm in poor surgical risk patients)
- Expansion >0.5 cm/6 months
- Symptoms occur
• Poor surgical risk patients
- Class III-IV angina; LVEF 30%; recent CHF or MI; severe valve disease
- Serum creatinine >3 mg/dL
- PaO2 50 mm Hg; FEV1IL
- Cirrhosis with ascites
- Diffuse retroperitoneal fibrosis; hostile abdomen
- Physiologic age > chronological age
• Endovascular aneurysm repair
- There are currently 3 devices approved by the FDA for marketing. Late complications of these devices continue to occur.
- Long-term CT surveillance is required.
- Adequate iliac/femoral access
- Infrarenal non-aneurysmal neck length of at least 1 cm at the proximal and distal ends of the aneurysm
- Morphology suitable for endovascular repair
- One of the following: A diameter >5 cm, a diameter of 4-5 cm, and an increase in size by 0.5 cm in the past 6 months.
- Health status adequate to undergo the 2-hour plus implementation procedure
FOLLOW-UP
PROGNOSIS
• Aneurysms usually expand over time (Laplace's Law: T (wall tension) = Pressure  Radius. Wall tension is directly related to blood pressure and the radius of the artery.) When wall tension exceeds wall tensile strength, rupture occurs.
• Surgical Outcomes:Morbidity 32%; cardiac (MI) 11%; mortality 4.2%
• Risk of morbidity and mortality increase with age
• Operative mortality is inverse to surgeon volume, hospital volume, specialty (vascular vs general surgeon)
• Non-repair (natural history of AAA >5.5 cm); 57% mortality within 1.5 years
• Mean expansion is 0.4 cm per year
• Rupture risk is increased by:
- Diastolic hypertension
- Tobacco use
- Diameter >6 cm
- COPD
- Familial history
• Ruptured aneurysms
- 8% die before receiving definitive care and 50% of the remaining die during their treatment or hospitalization.
COMPLICATIONS
• Rupture
• Associated dissection
• Thrombosis
• Embolization distally
PATIENT MONITORING
• Hypertension control
• Lipid control
• Recurrent assessment of smoking status
• Perioperative complications
- MI: 5%
- Renal failure: 6%, chronic dialysis: 1%
- Pulmonary failure: 5-8%
- Microembolism (trash foot): 1-4%
- Ischemic colitis: 0.5-1%
- Wound infection: 2%
- Graft infection: 0.5%
- Stroke: 0.5-1%
- Paraplegia: 0.2%
• Postsurgical monitoring
- Anastomotic aneurysm
- Graft infections
- Aortoenteric fistula
- Graft limb occlusion
- Additional aneurysms: Thoracic, thoracoabdominal, femoral
REFERENCES
1. Irvin TT. Abdominal pain: A surgical audit of 1190 emergency admissions. Br J Surg. 1989;76:1121.
2. Johnston W, Rutherford RB, Tilson MD, et al. Suggested standards for reporting on arterial aneurysms. J Vasc Surg. 1991;13:452.
3. Lederle FA, Wilson SE, Johnson GR, et al. Aneurysm detection and management Veterans Affairs cooperative study group. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1437-1444.
4. Mason JJ, Owens DK, Harris RA, Cooke JP, Hlatky MA. The role of coronary angiography and coronary revascularization before non-cardiac vascular surgery. JAMA. 1995;273:1919.
5. Porter JM, ed. The Year Book of Vascular Surgery. New York, NY: Mosby-Year Book; 1997.
6. Rutherford B, ed. Vascular Surgery. 14th ed. Philadelphia: WB Saunders; 1995.
7. Szilagyi DE, Smith RF, DeRusso FJ, Elliott JP, Sherrin FW. Contribution of abdominal aortic aneurysmectomy to prolongation of life. Ann Surg. 1966;164:678.

ANEMIA, SIDEROBLASTIC

2008-12-31T01:26:00.000-08:00

ANEMIA, SIDEROBLASTIC - Anne C. Nofziger, MD
BASICS
DESCRIPTION
A heterogeneous group of disorders characterized by microcytic, hypochromic anemia, impaired heme biosynthesis causing ineffective erythropoiesis, and ringed sideroblasts in the bone marrow. Severity and course may range from severe progressive to indolent asymptomatic anemia; onset may be congenital or late in life.
GENERAL PREVENTION
Pyridoxine prophylaxis with INH therapy
EPIDEMIOLOGY
• As a group, sideroblastic anemias (SA) are uncommon, and specific incidence/prevalence information is difficult to find.
• Acquired forms more common than hereditary forms (1), usually occur in older adults; present in 25-30% of alcoholics with anemia (2)
• Several hundred X-linked cases described (3) Hereditary forms variably severe, usually manifest in childhood
RISK FACTORS
• Male gender (X-linked SA)
• Family history of hereditary SA
• Chronic alcohol abuse
• Gastric bypass surgery (1 case report) (4)
Genetics
• Usually X-linked
- Defect in aminolevulinic acid synthase (ALAS-2 mutation), the first and rate-limiting enzyme in heme biosynthesis
- With congenital ataxia: hABC7 gene mutations (mitochondrial transport protein)
• Rarely autosomal dominant or recessive; gene(s) unknown
• Mitochondrial cytopathy
- Heterogeneous, involve deletions in mtDNA
- Unpredictable maternal inheritance
• See "Etiology"
PATHOPHYSIOLOGY
• Impaired heme biosynthesis within mitochondria
• Ineffective erythropoiesis
• Increased GI absorption of iron (Fe overload)
• Enhanced apoptosis in bone marrow
• Possibly, reactive oxygen species play a role
ETIOLOGY
Acquired SA
• Reversible
• Drugs and toxins
- Ethanol (SA is a later finding in multifactorial anemia related to alcoholism)
- INH
- Chloramphenicol
- Cycloserine
- Zinc toxicity (Cu deficiency)
• Nutritional deficiencies
- Pyridoxine deficiency
- Copper deficiency
 Post-gastrectomy
 Prolonged parenteral nutrition
 Prolonged zinc supplementation
• Hypothermia
• Acquired idiopathic sideroblastic anemia (AISA)
- Pure sideroblastic anemia (PSA)
 Only the erythroid line affected
- Refractory anemia with ringed sideroblasts (RARS)
 Myelodysplasia, other cell lines also affected
- Associated with hematologic malignancies, myeloproliferative disorders
Hereditary SA
• X-linked
• Autosomal dominant, recessive, maternal inheritance
• Mitochondrial cytopathy
- Wolfram syndrome
- Pearson syndrome
Congenital SA
Disproportionately male, sporadic, mild to severe, kindreds too small to analyze inheritance
ASSOCIATED CONDITIONS
• Alcoholism
• According to mutation, e.g., severe congenital ataxia (hABC7 mutation), pancreatic dysfunction (Pearson syndrome)
• Iron overload or "erythropoeitic hemochromatosis" (2) develops over time in all but reversible and x-linked/ataxia forms.
• Rarely, coexisting iron deficiency masks SA.

DIAGNOSIS
PRE HOSPITAL
Often an incidental finding
SIGNS AND SYMPTOMS
• Moderate to severe anemia
- Fatigue
- Dizziness
- Diminished exercise tolerance
- More symptomatic in older patients with comorbid conditions
• Specific to cause
- Pyridoxine deficiency (peripheral neuropathy, dermatitis)
- Alcoholism
• Manifestations of iron overload
History
• Toxin or drug exposures
• Family history of anemia, especially in men
Physical Exam
• No pathognomonic physical findings
• Mild-moderate hepatosplenomegaly at diagnosis in 1/3-1/2 of patients with AISA (2)
TESTS
Lab
• CBC
- Low MCH
- Low MCHC
- Low MCV (may be normal or high, esp. in myelodysplasia)
- High RDW
- Hgb highly variable
- Siderocytes in peripheral smear (occasional)
- WBC normal; may be reduced if hypersplenism, myelodysplasia
- Platelets normal; may be reduced if hypersplenism, myelodysplasia
- Low reticulocyte count
• Iron studies
- Ferritin increased
- Transferrin saturation increased
- Serum transferrin decreased
- Reticuloendothelial iron increased
• Serum copper, ceruloplasmin, serum zinc if suspected as cause
• Liver enzyme derangements possible depending on cause (EtOH, cirrhosis, Fe overload)
• Molecular studies identify specific mutations causing hereditary SA syndromes
• Myelodysplasia: Morphologic and cytogenetic evaluation required for prognosis
Diagnostic Procedures/Surgery
• Bone marrow examination confirms diagnosis of SA
• Liver biopsy is best; test to assess degree of iron overload.
• See "Pathological Findings"
Pathological Findings
• Bone marrow examination is the key diagnostic modality (1)[C]
- Normoblastic erythroid hyperplasia
- Perls' Prussian blue iron stain: Ringed sideroblasts, >10% of erythroblasts with increased number of abnormally large granules ringing the nucleus
- Electron microscopy: Iron-overloaded mitochondria within erythroblasts
- Iron-laden macrophages
• Liver biopsy
- Iron deposition as in hereditary hemachromatosis
- Micronodular cirrhosis by 3rd or 4th decade
DIFFERENTIAL DIAGNOSIS
• Thalassemias
• Iron deficiency anemia
• Anemia of chronic disease
• Myelodysplastic syndromes
• Lead toxicity with anemia
TREATMENT
GENERAL MEASURES
Treatment is largely supportive
• Pyridoxine supplementation improves symptoms in responsive cases (1)[B]
• Eliminate toxins, causative drugs
• Periodic transfusion: Maintain acceptable hemoglobin to alleviate symptoms and allow normal growth and development (children) (1)[B]
• Prevent end-organ damage from severe iron overload (1)[B]
- Phlebotomy preferred modality if anemia is mild or moderate
- Iron chelation in patients with more severe anemia, or requiring more transfusions
Diet
Address relevant nutritional deficiencies
Activity
As tolerated
SPECIAL THERAPY
Allogeneic stem cell transplantation has been successful in a few cases in younger patients with myelodysplastic syndromes.
IV Fluids
RBC transfusion when necessary
MEDICATION (DRUGS)
First Line
• Trial of pyridoxine is indicated because it has few drawbacks and is very beneficial in responsive cases (1)[B]
- Pyridoxine 50-100 mg PO daily
- Maintenance: Minimum dose to maintain acceptable hgb.
- Supplement folate to compensate for increased erythropoiesis if effective
- Response likely if SA caused by alcohol abuse, pyridoxine antagonists, or some forms of hereditary x-linked SA.
• Chelation therapy for iron overload (1)[B]
• Deferoxamine 40 mg/kg/d in continuous 12-24-hour daily infusions
- Limit ascorbate intake to 200 mg/d
- Auditory/visual toxicity very rare
• Defirasirox is a new oral once-daily iron chelator
- No long-term safety data
- Main complications skin rash, GI upset
• Goal of therapy is to maintain serum ferritin 500 ug/L
Second Line
• Myelodysplasia: PSA and RARS
• Treatment considerations as above, though no expected response to pyridoxine
• Some respond to combination of erythropoeitin (EPO) and granulocyte colony-stimulating factor (G-CSF) (1)[C]
• Chemotherapeutic agents may have a role.
SURGERY
• Splenectomy is contraindicated due to frequent postoperative thromboembolic complications (2)[B].
FOLLOW-UP
DISPOSITION
Admission Criteria
Generally managed in outpatient settings except for treatment of complications such as CHF, dysrhythmias.
Issues for Referral
• Hematology consultation is helpful for diagnosis and management, particularly if no reversible cause identified.
• Genetic counseling is important for patients with heritable cause of SA.
PROGNOSIS
• 75% of x-linked SA with ALAS-2 mutations are pyridoxine responsive (2)
• Prognosis better if iron overload prevented
• Aquired Idiopathic SA:
- RARS: 1- and 5-year cumulative risk of acute leukemia are 20% and 38%, respectively (1)
- When only the erythroid line is affected (PSA), course as in age-matched controls, transformation to leukemia not observed. (2)
- If SA follows treatment for malignancy, leukemic transformation is common.
COMPLICATIONS
• Iron overload causing organ damage
- Cardiac arrhythmia or CHF
- Hepatic dysfunction
• Transfusion complications
PATIENT MONITORING
• Yearly ferritin and transferrin saturation to monitor for Fe overload
• Follow response to treatment: Reticulocytosis within 2 weeks, improved hgb within 1-2 months of response to pyridoxine, and correction of nutritional deficiency or withdrawal of reversible cause.
REFERENCES
1. Alcindor T, Bridges KR. Sideroblastic anaemias. Br J Haematol. 2002;116:733-743.
2. Bottomley SS. Sideroblastic anemias. In: Greer JP, Foerster J, Lukens J, et al., eds. Wintrobe's Clinical Hematology, 11th ed. Philadelphia: Lippincott, Williams and Wilkins; 2004.
3. http://ghr.nlm.nih.gov/ghr/ accessed February 2006
4. Almhanna K, Khan P, Schaldenbrand M, Momin F. Sideroblastic anemia after bariatric surgery. Am J Hematol. 2006;81(2):155-156.
ADDITIONAL READING
• See http://www.genetests.org for counseling information on specific heritable SA syndromes and availability of testing.
• http://ghr.nlm.nih.gov/condition=xlinkedsideroblasticanemia

ANEMIA, SICKLE CELL

2008-12-31T01:24:00.000-08:00

ANEMIA, SICKLE CELL - Diane M. Haleem, PhD, RN
BASICS
DESCRIPTION
• A chronic hemoglobinopathy transmitted genetically; marked by moderately severe chronic hemolytic anemia, periodic acute episodes of painful "crises," and increased susceptibility to intercurrent infections, especially Saccharomyces pneumoniae.
• The heterozygous condition (Hb A/S) is called sickle cell trait and is usually asymptomatic with no anemia.
• System(s) Affected: Hematologic, Lymphatic/immunologic; Musculoskeletal
• Synonym(s): Sickle cell disease; Hb S disease
ALERT
Pediatric Considerations
• Sequestration crises and hand-foot syndrome seen only in infants/young children
• Functional asplenia in later childhood
• Adolescence/young adulthood
- Frequency of complications and organ/tissue damage increase with age (except for strokes, which occur mostly in childhood).
- Psychological complications: Body-image and sexual identity problems, interrupted schooling, career, restriction of activities, stigma of disease, low self-esteem
• Consider periodic transcranial Doppler ultrasound in all children ages 2-16
Pregnancy Considerations
• Usually complicated and hazardous, especially 3rd trimester and delivery
• Increased risk of crises, toxemia, infection, pulmonary infarction, phlebitis
• Fetal mortality 35-40%
• Partial exchange transfusion in 3rd trimester reduces maternal morbidity and fetal mortality.
• Chronic transfusions have been effective in diminishing episodes in pregnant women.
GENERAL PREVENTION
• Avoid conditions that precipitate sickling (hypoxia, dehydration, cold, infection, fever, acidosis, anesthesia).
• Granulocyte colony-stimulating factor is absolutely contraindicated.
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
• ~1/500 African Americans and 1/1,000 Hispanics have sickle cell anemia.
• 10% African Americans have sickle trait.
• To a lesser extent, people from the Middle East, Mediterranean area, and aboriginal tribes in India
RISK FACTORS
• Vaso-occlusive crisis
- Hypoxia
- Dehydration, fever
- Infection
- Acidosis, cold
- Anesthesia
- Strenuous physical exercise
- Smoking
• Aplastic crisis
- Severe infections
- Human parvovirus B19 infection
- Folic acid deficiency
• Hyperhemolytic crisis
- Acute bacterial infections
- Exposure to oxidant drugs
Genetics
• Autosomal recessive, mostly in African Americans.
• Homozygous presence of a variant hemoglobin, Hb S, or sickle hemoglobin
• Heterozygous condition Hb A/S
ETIOLOGY
• At molecular level: Hb S is produced by substitution of valine for glutamic acid in the 6th amino acid position of the -chains of the hemoglobin molecule. When deoxygenated, Hb S polymerizes and forms long rods that change RBC from biconcave to sickle shape.
• At cellular level: Sickle RBCs are inflexible; their odd shape and cell rigidity cause increased blood viscosity, stasis, mechanical obstruction of small arterioles and capillaries, and ischemia. Sickle RBCs are fragile, leading to hemolysis.
• At clinical level: Chronic anemia; "crises";
- Vaso-occlusive crisis ("painful crisis"): Most common; pain results from tissue necrosis secondary to vascular occlusion and tissue hypoxia. Progressive organ failure and acute tissue damage result from repeated vaso-occlusive episodes.
- Aplastic crisis: Suppression of RBC production by severe infection
- Hyperhemolytic crisis: Accelerated hemolysis; increased RBC fragility/shortened lifespan
- Sequestration crisis: Splenic sequestration of blood (only in infants/young children)
- Susceptibility to infection: Impaired/absent splenic function; defect in the alternate pathway of complement activation
ASSOCIATED CONDITIONS
The psychosocial effects can result in low self-esteem, depression, and dependency.

DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Chronic hemolytic anemia
• Mild scleral icterus
• Increased infection risk, i.e., pneumococcal sepsis and Salmonella osteomyelitis
• Functional asplenia by ~5-6 years of age
• Delayed physical/sexual maturation
Physical Exam
• After 6 months of age, earliest symptoms are pallor and symmetric, painful swelling of the hands and feet (hand-foot syndrome).
• Often asymptomatic in early months of life
• Painful "crises" in bones, joints, abdomen, back, and viscera (90% of all hospital admissions)
• Acute chest syndrome SS tachycardia, fever, bilateral infiltrates caused by decrease in hemoglobin and infarction of pulmonary vasculature (clinical picture consistent with pneumonia and/or infection)
• Many multisystem complications, especially in later childhood and adolescence
TESTS
Lab
• Hb electrophoresis
• Sickle cell anemia (FS pattern): 80-100% Hb S, variable amounts of Hb F and no Hb A. Sickle cell trait (FS pattern): 20-40% Hb S, 60-80% Hb A1, minimal Hb F.
• Screening tests: Sodium metabisulfite reduction test; "Sickledex" test
• Hemoglobin approximately 8 g/dL (1.24 mmol/L); RBC indices usually normal, but mean corpuscular volume (MCV) >75 m3 (>75 fL)
• Reticulocytosis of 10-20%
• Leukocytosis; bands in absence of infection
• Thrombocytosis
• Peripheral smear: Sickled RBCs, nucleated RBCs, Howell-Jolly bodies
• Serum bilirubin mildly elevated (2-4 mg/dL [34-68 mol/L]); fecal/urinary urobilinogen high
• ESR low
• Serum LDH elevated
• Haptoglobin absent or very low
• Disorders that may alter lab results: Infection
Imaging
• Bone scan (to rule out osteomyelitis)
• CT/MRI (to rule out CVA)
• Chest radiograph: May show enlarged heart; diffuse alveolar infiltrates in acute chest syndrome
• Transcranial Doppler: Start at age 2; repeat yearly (1,2,3)[B]
• Echocardiography to detect pulmonary hypertension (2,3)[C]
Pathological Findings
• In moderate to severe cases, hyposplenism due to autosplenectomy is common.
• Hypoxia/infarction in multiple organs
DIFFERENTIAL DIAGNOSIS
• Anemia: Other hemoglobinopathies (e.g., Hb SC disease, Hb C disease, sickle cell- thalassemia)
• Painful crises: Other causes of acute pain in bones, joints, and abdomen
TREATMENT
STABILIZATION
General health maintenance: Assessment of growth/development, regular immunizations, vision/hearing screening, and dental care
GENERAL MEASURES
• Infections/fever: Treatment with antibiotics
• Minimize factors that enhance sickling
• Painful crises: Hydration (2X maintenance fluids); analgesics; oxygen if hypoxic
• Transfusion needed with aplastic crises, severe complications (i.e., CVA), before surgery
• Retinal evaluation starting at school age to detect proliferative sickle retinopathy
• Occupational therapy
• Cognitive and behavioral intervention: Include distraction, relaxation, and motivational therapy
• Support groups
• Special immunizations (1,3)[B]
- Influenza vaccine yearly starting at age 2
- Heptavalent conjugated pneumococcal vaccine at 2, 4, 6 months; booster at 15 months, 2 years, 5 years
- 23-valent pneumococcal vaccine at 2 years; booster at age 5; always separate this by 8 weeks from heptavalent vaccine
- Meningococcal vaccine after age 2
Diet
• Folic acid supplementation
• Avoid alcohol (leads to dehydration)
Activity
Bed rest with crises
Physical Therapy
To include heat, massage, and exercise
IV Fluids
2X maintenance fluids (NS preferred) for severe painful crises (2)[C]
MEDICATION (DRUGS)
First Line
• Supplemental oxygen
• Painful crises (mild, outpatient)
- Nonnarcotic analgesics (ibuprofen, tramadol) (1,2,3)[C]
• Painful crises (severe, hospitalized) (1,2,3)[B]
- Parenteral narcotics (e.g., morphine on fixed schedule); (PCA pump may be useful.)
- Corticosteroids (dexamethasone 0.3 mg/kg q12h for 4 doses in children) may be used for painful crisis or chest syndrome.
• Prevention of painful crisis
- Hydroxyurea (increases hemoglobin F levels thus decreasing permanent formation of sickle cells.) in adult patients with 3 crisis/year. Start with 15 mg/kg/d single daily dose; titrate upward every 12 weeks if blood counts satisfactory. Increase in 5 mg/kg increments to maximum of 35 mg/kg/d. Reduces crisis and chest syndrome 50%; long-term safety unknown. Contraindicated in pregnancy (2-4)[A].
- Inhaled nitric oxide, arginine butyrate (has anti-sticking properties; may enhance availability of nitric oxide) and combination of erythropoietin with hydroxyurea (2,4)[B].
• For infections prior to culture results (2,3)[C], prescribe an antibiotic that covers S. pneumoniae, H. influenzae, mycoplasma pneumoniae, and Chlamydia pneumoniae. If osteomyelitis, cover for Staphylococcus aureus and Salmonella.
• Prophylactic penicillin is indicated in all infants and children starting at 2 months (1,4)[A].
- For 2-6 months of age: 62.5 mg b.i.d.
- For 6 months-3 years: 125 mg b.i.d.
- For 3-5 years: 250 mg b.i.d.
- If no pneumococcal infections and no splenectomy stop at 6 years; if high risk remains, continue until puberty.
- Alternative penicillin, benzathine IM 300,000 U/mo, ages 4 months-3 years, then 600,000 U/mo for 3-5 years
- Rising pneumococcal resistance to penicillin may change future recommendations.
• Precautions: Avoid high-dose estrogen oral contraceptives; consider Depo-Provera.
Second Line
• Other NSAIDs
• Folic acid supplements (1,3)[C]
- From 0-6 months: 0.1 mg/d
- From 6-12 months: 0.25 mg/d
- From 1-2 years: 0.5 mg/d
- Beyond age 2: 1 mg/d
SURGERY
Bone marrow transplantation is curative, but the availability is limited.
FOLLOW-UP
DISPOSITION
Admission Criteria
Severe pain, suspected infection or sepsis
PROGNOSIS
• Anemia is lifelong. In 2nd decade of life, patient usually experiences fewer crises, but complications are more frequent. Median age of death is 42 for men and 48 for women. Common causes are infections, thrombosis, pulmonary emboli, pulmonary hypertension, and renal failure.
• Children become anemic at infancy and begin to have sickle cell crisis at 1-2 years of age; some children die in their 1st year.
COMPLICATIONS
• Alloimmunization
• Bone infarct
• Aseptic necrosis of femoral head
• Cerebrovascular accidents (peak age 6-7)
- In the 10% of patients who suffer these, transfusions q3-4 weeks will reduce the risk by 90%. Initiate based on abnormal transcranial Doppler. May require iron chelation therapy.
• Cardiac enlargement
• Pulmonary hypertension
• Cholelithiasis/abnormal liver function
• Chronic leg ulcers
• Poor wound healing
• Impotence
• Priapism
• Hematuria/hyposthenuria
• Renal concentrating and acidifying defects
• Retinopathy
• Acute chest syndrome (infection/infarction), leading to chronic pulmonary disease
• Infections (pneumonia, osteomyelitis, meningitis, pyelonephritis); sepsis
• Hemosiderosis (2 to multiple transfusions)
• Decreased intelligence, even without stroke
• Splenic infarction can occur by 10 years of age.
• Substance abuse related to chronic pain
PATIENT MONITORING
• Determined by number/severity of crises
• It is important to recognize and treat infections early. Parents and patients should be instructed that a temperature of 101F (38.3C) requires immediate medical attention.
• All febrile patients require cultures (blood/urine), chest radiograph, and CBC/reticulocytes.
• For patients who receive chronic transfusions, monitor for hepatitis and hemosiderosis.
• Begin periodic eye evaluations at age 5 to detect proliferative sickle retinopathy (1,3)[C].
REFERENCES
1. American Academy of Pediatrics, Section on Hematology/Oncology. Health supervision of children with sickle cell disease. Pediatrics. 2002;109:526-535.
2. Johnson CS, ed. Sickle cell disease. Hematol Oncol Clin North Am. 2005;19(5).
3. National Institutes of Health. The management of sickle cell disease, 4th ed. 2002. NH Publ# 02-2117.
4. Bonds DR. Three decades of innovation in the management of sickle cell disease. Blood Rev. 2005;19:99-110.
5. Stop Trial Investigators. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005;353(26):2769-2778.
6. Fischbach F. Nurse's Quick Reference to Common Laboratory and Diagnostic Tests, 3rd ed. Philadelphia: Lippincott, 2002.
7. Smeltzer SC, Bare BG, Hinkle JL, Cheever KH. Brunner  Suddarth's Textbook of Medical-Surgical Nursing, 11 ed. Philadelphia: Lippincott Williams  Wilkins, 2005.
8. Vichinsky EP. Pulmonary hypertension in sickle cell disease N Engl J Med. 2004;350(9):857-859.
9. Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004;364(9442):1343-1360.

ANEMIA, PERNICIOUS

2008-12-31T01:22:00.000-08:00

ANEMIA, PERNICIOUS - Abdulrazak Abyad, MD, PhD, MBA, MPH, AGSF
BASICS
DESCRIPTION
Pernicious anemia is a disorder due to vitamin B12 deficiency. It is invariably associated with atrophic gastritis and histamine-fast achlorhydria. Vitamin B12 cannot be absorbed in the terminal ileum without intrinsic factor (a secretion of the parietal cells of the gastric mucosa). Its usual course is slowly progressive.
• System(s) Affected: Gastrointestinal; Hematologic/Lymphatic/Immunologic; Nervous
• Synonym(s): Addison anemia; Megaloblastic anemia due to B12 deficiency
ALERT
Geriatric Considerations
More common in this age group and often in association with other autoimmune disorders, depression, and dementia
Pediatric Considerations
• Juvenile pernicious anemia occurs in older children and is the same in most respects as in adults.
• Congenital pernicious anemia is usually evident before 3 years of age.
Pregnancy Considerations
Untreated pernicious anemia in pregnancy may cause neural tube defects.
GENERAL PREVENTION
• Early detection of anemia
• Workup of anemia
EPIDEMIOLOGY
Predominant sex: Male = Female
Incidence
Unknown
Prevalence
Older adults (>60 years)
RISK FACTORS
• Vegetarian diet, without B12 supplementation
• Gastrectomy
• Blind loop syndrome
• Fish-tapeworm infestation
• Malabsorption syndromes
• Drugs: Oral calcium-chelating drugs, amino salicylic acid, and biguanides
• Chronic pancreatitis
• Alcoholism
Genetics
• HLA-DR2, HLA-DR4: Present in the rare form of pernicious anemia that is hereditary
• Endemic area: Northern Europe, including Scandinavia
ETIOLOGY
• Atrophic gastric mucosa
• Intrinsic factor deficiency
• Probable autoimmunity against gastric parietal cells
• Autoimmunity against intrinsic factor
ASSOCIATED CONDITIONS
• Autoimmune diseases including rheumatoid arthritis, IgA deficiency
• Graves disease
• Myxedema
• Iron deficiency
• Thyroiditis
• Vitiligo
• Idiopathic adrenocortical insufficiency
• Hypoparathyroidism
• Agammaglobulinemia
• Tropical sprue
• Celiac disease
• Crohn's disease
• Infiltrate disorders of the ileum and small intestine

DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Anorexia, weight loss
• Depression
• Position sense: Decreased
• Prematurely gray-haired
• Tinnitus
Physical Exam
• Abnormal reflexes
• Ataxia
• Atrophic glossitis
• Babinski's sign: Positive
• Confusion
• Congestive heart failure
• Dementia
• Exertional dyspnea
• Extremity numbness
• Extremity paresthesias
• Hepatomegaly
• Hypoalqesia in "sock and glove" distribution
• Pallor
• Palpitations
• Poor finger coordination
• Purpura
• Romberg's sign: Positive
• Skin pigmentation increased
• Sore tongue
• Splenomegaly
• Tachycardia
• Vertigo
• Vibration sense: Decreased
• Vitiligo
• Weakness
TESTS
• Schilling test plus intrinsic factor: Normal vitamin B12 absorption
• Schilling test: Decreased vitamin B12 absorption
• Gastric analysis: Achlorhydria
Lab
• Achlorhydria
• Anisocytosis
• Haptoglobin decreased
• Howell-Jolly bodies
• Hypergastrinemia
• Hypersegmented neutrophils
• LDH increased
• Leukopenia
• Macrocytic anemia; MCV: 110-140
• Pentagastrin stimulation: Stomach pH >6
• Serum ferritin increased
• Serum vitamin B12 level 100 pg/mL (74 pmol/L)
• Peripheral blood smear: Macro-ovalocytes
• Poikilocytes
• Thrombocytopenia
• Anti-intrinsic poikilocytosis factor antibody
• Anti-parietal cell antibody
• Direct hyperbilirubinemia
• Disorders that may alter lab results
- Falsely elevated MCV
 Cold agglutinins
 Hyperglycemia
 Marked hyperleukocytosis
- Falsely normal serum vitamin B12 level
 Myeloproliferative disorders
 Liver disease
- Falsely low serum B12 level
 Multiple myeloma
 Oral contraceptive intake
 Pregnancy
 Folate deficiency
 Transcobalamin I deficiency
 Recent isotope administration
Diagnostic Procedures/Surgery
• Bone marrow aspiration
• Detailed history and physical exam
Pathological Findings
• Bone marrow: Hypercellular, macrocytes, iron stores increased
• Nests of megaloblasts
• Giant metamyelocytes
• Macro-polymorpho-leukocytes
• Hypersegmented neutrophils
• Stomach: Atrophic gastritis, goblet cells increased
• Parietal cell atrophy
• Chief cell atrophy
• Gastric cytology: Cellular atypia
• Spinal cord: Myelin degeneration of the dorsal and lateral tracts
• Peripheral nerve degeneration
• Degenerative changes of the posterior root ganglia
DIFFERENTIAL DIAGNOSIS
• Folic acid deficiency
• Myelodysplasia
• Neurological disorders without B12 deficiency
• Liver dysfunction
• Hypothyroidism
• Hemolysis or bleeding
• Drug effects
• Alcoholism
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient
• Treatment must be continued for life
• Identification and treatment of the underlying disorder
ALERT
Folic acid treatment without vitamin B12 in patients with pernicious anemia is contraindicated.
Diet
Emphasize meat, animal protein foods, and legumes unless contraindicated.
Activity
Unlimited
MEDICATION (DRUGS)
• Parenteral Vitamin B12 (cyanocobalamin)
- 1,000 mcg SQ for each dose
- Administer daily for the 1st week
- Administer weekly for 1 month
- Monthly injections for remainder of life (patients may be taught to give self-injection)
• Precautions: Do not give folic acid supplements without vitamin B12, may cause fulminant neurological deficit.
FOLLOW-UP
PROGNOSIS
• Anemia reversible with parenteral vitamin B12
• Neurologic effects not reversible with parenteral vitamin B12
COMPLICATIONS
• Hypokalemia may complicate the 1st week of treatment.
• Central nervous system symptoms may be permanent if patient is not treated in 6 months after the symptoms begin.
• Gastric polyps
• Stomach cancer
- There is a 3-fold likelihood of developing gastric carcinoma.
- Suggest endoscopy approximately every 5 years even if asymptomatic.
PATIENT MONITORING
• Monthly injections of vitamin B12
• Endoscopy every 5 years to rule out gastric carcinoma
REFERENCES
1. Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: WB Saunders; 1996.
2. Chui CH, Lau FY, Wong R, et al. Vitamin B12 deficiency-need for a new guideline. Nutrition. 2001;17:917-920.
3. Wheby MS, ed. The Medical Clinic of North America: Anemia. Vol. 76. Philadelphia, PA: WB Saunders; 1992.
4. Williams WJ, Beutler E, Erslev AJ, et al., eds. Hematology. 4th ed. New York, NY: McGraw-Hill; 1990.
MISCELLANEOUS
See also: Tropical Sprue

ANEMIA, IRON DEFICIENCY

2008-12-31T01:20:00.000-08:00

ANEMIA, IRON DEFICIENCY - Bruce Block, MD
BASICS
DESCRIPTION
• Anemia due to decreased iron stores
• Poor iron utilization and poor iron re-utilization (e.g., anemia of chronic disease) are also due to iron deficiency, but iron stores are not depleted.
• Onset may be acute with rapid blood loss or chronic with poor diet or slow blood loss.
• Most common cause of anemia in the United States.
• System(s) Affected: Hemic/Lymphatic/Immunologic
• Synonym(s): Anemia of chronic blood loss; Hypochromic; Microcytic anemia; and Chlorosis
ALERT
Geriatric Considerations
60% of anemias in people >65 years
Pediatric Considerations
Frequent problem in infants whose major source of nutrition is cow's milk and juices.
Pregnancy Considerations
Common during pregnancy unless iron supplements are included in the diet.
GENERAL PREVENTION
• Good nutrition with adequate iron intake
• Correction of gynecologic or other problems causing excess blood loss
EPIDEMIOLOGY
• Predominant age: All ages, but especially toddlers and menstruating women.
• Predominant sex: Female > Male
Incidence
• Adults: 7-10%
• Infants and toddlers: 10-20%
• Pregnant patients: 15-45%
Prevalence
• Most likely in the poor and in underimmunized children
ETIOLOGY
• Blood loss (e.g., menses, GI bleed)
• Poor iron intake
• Poor iron absorption (e.g., postgastrectomy)
• Increased demand for iron (e.g., infancy, adolescence, and pregnancy)
• Hookworm infestation
• Gastric carcinoma

DIAGNOSIS
SIGNS AND SYMPTOMS
• Asymptomatic in most cases
• Cheilosis
• Dyspnea on exertion, fatigue, tachycardia, palpitation, or vasomotor disturbances
• Effects of underlying GI ulceration, neoplasm, uterine disorders, or bleeding varices
• Headache, inability to concentrate, irritability, listlessness
• Neuralgic pain, peripheral paresthesias
• Pica (dirt, paint, ice)
• Spoon-shaped, brittle nails
• Susceptibility to infection
TESTS
• Stool guaiac; if positive, GI endoscopy, stool for O  P, clotting studies
• Rule out thalassemia: Review prior CBCs for persisting mild anemia and marked micro-ovalocytosis, elevated hemoglobin A2 or hemoglobin F, family history, and especially high or high normal RBC count
• Rule out G6PD deficiency: Assay at least 6 weeks after last drop in hemoglobin
• Rule out poor re-utilization: Trial of iron (oral or parenteral), bone marrow aspiration, and iron stain
• Rule out gastric carcinoma, especially in the elderly
Lab
• Ferritin, repeat CBC with differential, peripheral smear
• Stainable iron in bone marrow aspiration is the gold standard
• Low serum ferritin is the best noninvasive test in adults, but it may miss some deficient patients, because ferritin is an acute phase reactant.
• Fe/total iron binding capacity (transferrin ratio) is no longer recommended, because it is less sensitive and less specific than ferritin.
• A peripheral smear usually shows hypochromia and microcytosis, but may be normal.
• Hemoglobin is usually lower than 12 g/dL, but patients with higher premorbid hemoglobin (such as smokers and patients with chronic hypoxemia) may be anemic at higher hemoglobin levels. Abnormal values for infants and toddlers, and for pregnant persons, are 10.5-11.0 g/dL.
• A low RBC count in chronic bleeding helps to distinguish it from thalassemia trait where the count is high or high-normal.
• Microcytosis with ovalocytosis and anemia unresponsive to iron suggest the thalassemia trait.
• A low MCV may be absent in mild anemia, or hidden by the population of larger cells (e.g., reticulocytes or macrocytes).
• An empiric trial of iron at 3 mg/kg/d may be the best way to diagnose decreased iron stores in infants and children, if reticulocytes are elevated in 7-10 days or hemoglobin is increased >1.0 g/dL after 4 weeks.
• Drugs that may alter lab results: Iron supplements or multivitamin-mineral preparations that contain iron
• Disorders that may alter lab results:
- Ferritin elevated by acute liver disease, cirrhosis, Hodgkin disease, acute leukemia, solid tumors, fever, acute inflammation, renal dialysis
- Hemoglobin may be elevated by smoking or chronic hypoxemia, thereby hiding anemia if standard anemia limits are used.
Imaging
GI endoscopy to discover occult bleeding sites
Pathological Findings
• Absent marrow iron stores
• Marrow: Hyperplastic, micronormoblastic
DIFFERENTIAL DIAGNOSIS
• Bone marrow aspiration
• Sigmoidoscopy
• Gastroscopy
• Colonoscopy
• Defective iron utilization (e.g., thalassemia trait, sideroblastosis, G6PD deficiency)
• Defective iron re-utilization (e.g., infection, inflammation, cancer, other chronic diseases)
• Hypoproliferation (e.g., decreased erythropoietin from hypothyroidism, renal failure, etc.)
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Search for the cause and correct it. There can be no excuse for not searching for a bleeding site.
• Avoid transfusions except in rare cases.
Diet
• Limit milk to 1 pint a day (adults).
• Emphasize protein-containing and iron-containing foods (meat, beans, and leafy green vegetables).
• Increase dietary fiber to decrease likelihood of constipation during iron replacement therapy.
• Do not consume milk, other dairy products, antacids, or tetracycline within 2 hours of the drug dosage.
Activity
Patients with hypoxemia, low cardiac output, or angina may require reduced activity prescriptions.
MEDICATION (DRUGS)
First Line
• Ferrous sulfate 300 mg t.i.d. on an empty stomach 1 hour before meals is an ideal dose that provides 180 mg of elemental iron a day.
- Dose can be reduced as needed for GI symptoms, which affect 15% of patients on standard iron therapy, or the dose can be taken with meals, which may reduce the delivery of iron by 50%.
- People with a moderate anemia (hemoglobin = 10 g/dL) need only 1,500-2,000 mg of elemental iron replacement. Reducing the amount of iron per dose as much as necessary to abate symptoms will make parenteral iron therapy unnecessary in almost all cases.
- Special iron formulations and compounds are very expensive and reduce symptoms only to the degree that they reduce the delivery of iron.
• Liquid iron preparations are useful for children with a recommended dose of 3 mg/kg/d given in a single dose. They can be also used in adults when low tolerance to iron pills requires a reduction of dosage.
• Vitamin C provides acidification to reduce the iron and thus increases absorption.
• Continued bleeding is often the cause for "failure to respond" to iron.
• Consider parenteral iron for patients with malabsorption, if higher doses and use of vitamin C fail.
• Contraindications
- Antacids concomitantly
- Tetracycline concomitantly
• Precautions
- Iron preparations cause black bowel movements.
- Iron overdose is highly toxic. Patients should be instructed to keep tablets and liquids out of the reach of small children.
• Significant possible interactions
- Allopurinol
- Antacids
- Penicillamine
- Tetracyclines
- Vitamin E
FOLLOW-UP
PROGNOSIS
Curable with iron therapy if the underlying cause can be discovered and cured
COMPLICATIONS
Neglecting to identify hidden bleeding points, particularly a bleeding malignancy
PATIENT MONITORING
Regularly after return to normal (in order to detect recurrences)
REFERENCES
1. Adams WG, et al. Anemia and elevated lead levels in underimmunized inner-city children. Pediatrics. 1998;101.
2. Farrell R, LaMont JT. Rational approach to iron-deficiency anaemia in premenopausal women. Lancet. 1998;352:1953-1954.
3. Fireman Z, Kopelman Y, Sternberg A. Endoscopic evaluation of iron deficiency anemia and follow-up in patients older than age 50. J Clin Gastroenterol. 1998;26:7-10.
4. Lee RG, Bithell TC, et al. Wintrobe's Clinical Hematology. 9th ed. Philadelphia, PA: Lea  Febiger; 1993.
5. Van den Broek, et al. Iron status in pregnant women: Which measurements are valid? Br J Haematol. 1998;103:817-824.
6. Waterbury L. Anemia. In: Barker LR, Burton JR, Zieve PD, eds. Principles of Ambulatory Medicine. 4th ed. Philadelphia, PA: Lippincott Williams  Wilkins; 1995:593-607.
7. Williams WJ, Beutler E, Erslev AJ, et al., eds. Hematology. 4th ed. New York, NY: McGraw-Hill; 1990.

ANEMIA, AUTOIMMUNE HEMOLYTIC

2008-12-31T01:19:00.000-08:00

ANEMIA, AUTOIMMUNE HEMOLYTIC - Kerry J. Murphy, MD
BASICS
DESCRIPTION
• Acquired anemia induced by binding of autoantibodies to RBC membrane antigens
• 3 main types defined by maximal binding temperature of the autoantibodies
- Warm (37C [98.6F]) reacting IgG antibody
- Cold (0-4C [32-39.2F]) reacting IgM antibody
- Mixed type: Both warm IgG and cold C3 reacting antibodies
- Drug induced: Mostly warm IgG reacting antibodies
- System(s) Affected Hematopoietic/lymphatic/immunologic
GENERAL PREVENTION
None known
EPIDEMIOLOGY
• Predominant age: 50 years
• Predominant sex: Female > Male
ALERT
Geriatric Considerations
Unusual in this age group; rule out neoplasia.
Pediatric Considerations
May occur in pediatric age group
Incidence
4/100,000 per year
RISK FACTORS
• Malignancy
• Autoimmune disorders
• Infection
• Medications
• Prior blood transfusion
• Prior hematopoietic cell transplant
Genetics
Unknown
PATHOPHYSIOLOGY
• Warm autoimmune hemolytic anemia (AIHA)
- IgG attaches to RBCs, which are then ingested by macrophages of the spleen.
• Cold AIHA
- IgM binds RBC surface temporarily, activates complement, deposits C3 on cell surface, and RBCs are ingested by macrophages of the liver.
- Rarely, complete complement cascade activated with membrane attack complex insertion causing intravascular hemolysis.
• Mixed antibody AIHA: Both warm IgG and cold C3 involved.
• Drug induced
- Hapten induced: Drug attaches to rbc membrane inducing IgG production.
- Immune complex: Drug-IgM immune complex binds RBC membrane, activating complement.
- Autoantibody: Drug induces production of anti-RBC IgG.
ETIOLOGY
• Warm antibody (48-70% cases)
- Primary cause: Idiopathic
- Secondary causes
 Lymphoproliferative disorders (CLL, Hodgkin disease, NHL)
 Autoimmune disorders
 Viral infection (especially in children)
• Cold antibody
- Cold agglutinin syndrome (CAS) (16-32%):
 Acute: Infection (mycoplasma, mononucleosis, viral)
 Chronic: Lymphoproliferative disorders (lymphoma)
- Paroxysmal cold hemoglobinuria
 Infection
• Mixed type
- Idiopathic
- Secondary to lymphoproliferative or autoimmune disorders
• Drug induced
- Penicillin: Hapten induced
- Quinine: Immune complex
- -Methyldopa: Autoantibody induced
ASSOCIATED CONDITIONS
• Evans syndrome
• Systemic lupus erythematosus
• Chronic lymphocytic leukemia
• Diffuse lymphomas

DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Weakness/fatigue
• Exertional dyspnea
• Dizziness
• Palpitations
• Malaise
• Association with cold (CAS)
Physical Exam
• Pallor
• Jaundice
• Splenomegaly
• Hepatomegaly
• Tachycardia
• Flow murmur
• Blue gray discoloration of acral surfaces (CAS)
TESTS
Lab
• Direct Coombs' (DAT direct antiglobulin test)
- Positive test indicates presence of antibodies or complement on RBC surface.
• CBC
- Anemia (normocytic, normochromic); may be sudden and life threatening
- Mild to moderate increase in mean corpuscular volume (MCV) depending on level of reticulocytosis
- Increased mean cell hemoglobin concentration (MCHC)
- Spherocytosis
- Poikilocytosis
- Anisocytosis
- Rouleaux
- Reticulocytosis
- Nucleated RBC
- Large polychromatophilic reticulocytes
• Hyperbilirubinemia (unconjugated)
• Decreased haptoglobin
• Elevated LDH
• Hemoglobinemia
• Serology
- IgG antibody (warm, mixed, drug-induced, paroxysmal hemoglobinuria)
- IgM antibody (cold)
• Urinalysis
- Hemoglobinuria, hemosiderinuria
Pathological Findings
• Peripheral blood smear
- Spherocytes, schistocytes
• Bone marrow biopsy
- Bone marrow hyperplasia, increased marrow hemosiderin
DIFFERENTIAL DIAGNOSIS
• Other hemolytic anemias
• Autoimmune thrombocytopenic purpura (ITP)
• Evans syndrome
• Microangiopathic hemolytic disorders
• Aplastic anemia
• Megaloblastic anemia
TREATMENT
GENERAL MEASURES
• Warm antibody
- Folic acid supplementation
- Mild and moderate: See "Medications"
- Severe
 Plasmapheresis as a temporizing measure for refractory or life threatening anemia (1)[C]
 Packed RBC transfusion for life-threatening anemia (difficult to cross-match; need special blood bank techniques; in emergency, use most compatible cross-match (2)[C]
• Cold antibody
- Cold agglutinin syndrome
 Avoid cold, maintain high temperatures indoors, wear additional clothing outdoors
 Folic acid supplementation
 Plasmapheresis as a temporizing measure for refractory or life-threatening anemia (1)[C]
 Packed RBC transfusion for life-threatening anemia (2)[C]
• Paroxysmal cold hemoglobinuria
- Supportive care
• Mixed
- Steroids, splenectomy, and immunosuppressives as in warm AIHA
• Drug-induced
- Stop the offending drug.
- Plasmapheresis/exchange transfusion for severe life-threatening cases
Diet
No special diet
Activity
• Rest until asymptomatic.
• Avoid contact sports if splenomegaly is present.
MEDICATION (DRUGS)
First Line
• Warm antibody
- Glucocorticoids: Prednisone 1 mg/kg/d PO in divided doses
 70-80% patients improve within 3 weeks
 Taper gradually to 20 mg/d over 2 weeks
 May require maintenance dose 10 mg every other day (1)[A]
- Precautions: Significant side effects with long-term use
• Cold antibody
- Malignancy induced: Chemotherapy
- Rituximab for cold AIHA due to chronic lymphoproliferative disorders (1)[C]
• Mixed antibody
- Prednisone as in warm AIHA
Second Line
• Warm antibody
- Immunosuppressive drugs: Recommended for patients who fail splenectomy, relapse after splenectomy, cannot tolerate corticosteroids, and nonsurgical candidates
 Cyclophosphamide 50 mg/kg/d for 4 days followed by GCSF for those with refractory anemia (2)[C]
 Precautions: Monitor for marrow suppression
 Azathioprine (Imuran) 1-2 mg/kg/d within 2 weeks of starting steroids if not responding (3)[C]
 Cyclosporine 5-10 mg/kg/d in 2 divided doses
 Rituximab (anti-CD20 monoclonal Ab) 375 mg/m2 once weekly for 2-4 weeks for children and refractory cases
 Mycophenolate mofetil 500-1000 mg/d in 2 divided doses; increase to 1-2 g daily (2)[C]
- Other medical therapies for refractory cases
 Danazol 600-800 mg/d PO
 IVIG (1)[C]
• Mixed antibody
- Immunosuppressives if refractory to steroids and splenectomy
SURGERY
• Warm antibody
- Splenectomy is the preferred second-line treatment for warm AIHA for those who have failed steroids.
 50% initial response rate
 Patients may require low-dose maintenance prednisone 15 mg daily
 Post splenectomy: Vaccinate against encapsulated organisms such as pneumonococcus and meningococcus (2)[A]
• Cold antibody
- Surgery not recommended
• Mixed antibody
- Splenectomy
FOLLOW-UP
PROGNOSIS
• Good with appropriate treatment
• Determined by course of the primary disease If secondary to an underlying disorder
COMPLICATIONS
• Shock (severe anemia)
• Venous thromboembolism
• Thrombocytopenic purpura (Evans syndrome)
• Lymphoproliferative disorders in warm AIHA
• Post splenectomy sepsis syndrome
PATIENT MONITORING
• Monitor carefully if transfusion essential
• Use only warm IV fluids and blood products for cold AIHA
• Avoid hypothermic surgical procedures for cold AIHA
REFERENCES
1. Gehrs BC, Friedberg RC. Autoimmune hemolytic anemia. Amer J Hematol, 2002;69:258-271.
2. King KE, Ness PM. Treatment of autoimmune hemolytic anemia. Sem in Hematology, 2005; 42:131-136.
3. Pruss A, Salama A, Ahrens N, Hansen A, Kiesewetter H, Koscielny J, Dorner T. Immune hemolysis-serological and clinical aspects. Clin Exp Med, 2003;3:55-64.

ANEMIA, APLASTIC

2008-12-31T01:17:00.000-08:00

ANEMIA, APLASTIC - Angie N. Ross, MD
BASICS
DESCRIPTION
• Aplastic anemia is defined as pancytopenia and hypocellular bone marrow in the absence of abnormal cell infiltrate. The 2 forms of aplastic anemia include congenital and acquired.
• Congenital forms are seen mainly in the pediatric population and are associated with physical manifestations. The exception is an atypical presentation of Fanconi syndrome later in adult life, up to the 30s in males and up to 48 years in females.
• Acquired aplastic anemia has an insidious onset and is caused by exogenous insult triggering an autoimmune reaction. This form is usually responsive to immunosuppressive agents.
• System(s) affected: Hemic/lymphatic/immunologic
• Synonym(s): Hypoplastic anemia; Panmyelophthisis; Refractory anemia; Aleukia hemorrhagica; Toxic paralytic anemia
ALERT
• Prednisolone should not be used in treatment of patients with aplastic anemia (1)[C]
• Hematopoietic growth factors should not be used without close supervision in newly diagnosed patients (1)[C]
Geriatric Considerations
The elderly are more exposed to large numbers of drugs and, therefore, are more susceptible to secondary aplastic anemia.
Pediatric Considerations
• Congenital aplastic anemia requires a different treatment regimen (1)[B]
• Idiopathic aplastic anemia is more common in adolescents.
• Secondary aplastic anemia is seen in children exposed to ionizing radiation or treated with cytotoxic chemotherapeutic agents.
Pregnancy Considerations
Pregnancy may be rarely associated with aplastic anemia. Symptoms usual resolve after delivery. Supportive care is the mainstay and platelet count should be maintained above 20  109/L with platelet transfusion.
GENERAL PREVENTION
• Avoid possible toxic industrial agents.
• Use safety measures when working with radiation.
EPIDEMIOLOGY
• Predominant age
- Congenital: Children and young adults
- Acquired: Biphasic 10-25 and >60
• Predominant sex: Male = Female
Incidence
• 2 new cases per million in Europe and North America.
• The incidence is 3-fold in Thailand and China, when compared to the Western world
RISK FACTORS
• Viral illness/ Immunocompromised
• Toxin exposure
• Tumors of thymus (red cell aplasia)
Genetics
• A small number of patients with acquired and congenital forms have been found to have telomerase mutations. Mutations render carriers more susceptible to environmental insults to replicating stem cells. HLA-DR2 is twice as frequent than in the normal population.
• Autosomal recessive in congenital form
PATHOPHYSIOLOGY
• Injury to pluripotent stem cells causing markedly reduced hematopiesis and replacement of bone marrow by fat cells
• Current hypothesis supports stem cell destruction caused by activated autoimmune lymphocytes. Activation can arise from several causes mentioned below.
• Patients have high levels of interferon- gamma and fewer natural killer cells.
• Intact stromal function with normal to increased levels of cytokines and erythropoietin.
ETIOLOGY
• Idiopathic (~50% of the cases)
• Drugs (antibiotics, antirheumatics, anticonvulsants, chemotherapeutics, NSAIDs, sulfonamides.)
• Viral (HIV; EBV; postinfectious hepatitis-nonA, B, or C; parvovirus B19, mostly in the immunocompromised; atypical mycobacterium)
• Toxic exposure (benzene, pesticides, arsenic)
• Radiation exposure
• Immune disorders(systemic lupus erythematous, eosinophilic fascitis, graft versus host disease)
• Pregnancy (rare)
• Congenital (Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, amegakaryocytic thrombocytopenia)

DIAGNOSIS
SIGNS AND SYMPTOMS
History
Recurrent infections
Physical Exam
• Mucosal hemorrhage, petechiae
• Pallor
• Fatigue, fever
• Hemorrhage, menorrhagia, occult stool blood, melena, epistaxis
• Dyspnea
• Palpitations
• Progressive weakness
• Retinal flame hemorrhages
• Systolic ejection murmur
• Weight loss
• Congenital
- Short stature
- Microcephaly
- Radius and thumb anomalies
- Renal anomalies
- Skeletal anomalies
- Hyperpigmentation (cafe au lait spots)
- leukoplakia
TESTS
• Screening test to exclude other etiologies
• CBC and reticulocyte count
• Blood smear examination
- Cytogenetic studies of peripheral lymphocytes if 35 to exclude fanconi anemia
- Liver function test
- Viral serology: Hepatitis A, B, C, EBV, CMV, HIV
- Vitamin B12 and folate levels
- Autoantibody screening ANA and anti-DNA
- Flow cytometry or Ham test for PNH
- Fetal hemoglobin in children
- Red cell adenosine deaminase (pure red cell aplasia)
- Cytogenetic analysis of bone marrow
Lab
• Pancytopenia
• Anemia
• Leukopenia
• Neutropenia
• Thrombocytopenia
• Decreased reticulocytes
• Increased serum iron secondary to transfusion
• Normal total iron binding capacity (TIBC)
• Borderline high mean corpuscular volume (MCV) >104
• CD 34+ cells decreased in blood and marrow
• Hematuria
• Abnormal liver function tests (hepatitis)
• Increased fetal hemoglobin (Fanconi)
• Increased chromosomal breaks under specialized conditions (Fanconi)
• Molecular determination of abnormal gene (Fanconi)
Imaging
• CT of thymus region if thymoma-associated RBC aplasia suspected
• Radiographs of radius and thumbs (congenital anemia)
• Renal ultrasound (to rule out congenital anemia or malignant hematological disorder)
• Chest radiograph to exclude infection such as mycobacterial
Diagnostic Procedures/Surgery
Bone marrow aspirate and trephine biopsy
Pathological Findings
• Normochromic RBC
• Bone marrow
- Decreased cellularity (10%)
- Decreased megakaryocytes
- Decreased myelocytes
- Decreased erythroid precursors
- Prominent fat spaces
- Prominent lymphocytes, macrophages and plasma cells
DIFFERENTIAL DIAGNOSIS
• Myelodysplastic disorders and acute myeloid leukemia; dysplastic cells of the granulocytic and megakaryocytic lineages, blast cells in the marrow
• Paroxysmal nocturnal hemoglobinuria, hemolytic anemia (dark urine), pancytopenia venous thrombosis (classically hepatic veins)
• Acute lymphoblastic leukemia-neutropenia more pronounced than pancytopenia, may have an increase in reticulin in the bone marrow
• Hairy cell leukemia; increased reticulin and infiltration of hairy cells
• Systemic lupus erythematosus
• Lymphomas; gene rearrangements
• Prolonged starvation or anorexia nervosa; bone marrow is gelatinous with loss of fat cells and increased ground substance
• Transient erythroblastopenia of childhood
TREATMENT
STABILIZATION
Inpatient. Referral to an institution that has experience in treating these patients is recommended.
GENERAL MEASURES
• Supportive measures: RBC and platelet transfusions. Use only CMV negative blood initially if patient is candidate for BMT.
• Oxygen therapy for severe anemia
• Good oral hygiene
• Control menorrhagia with norethisterone
• Avoid causative agents/isolation if necessary
• Human leukocyte antigen (HLA) testing on all patients and their immediate families
• Transfusion support (judiciously prescribed RBCs for severe anemia, consider leukocyte depleted units; platelets for severe thrombocytopenia; WBCs)
- Transfuse when platelet count is 10  109 or if 20  109 with fever (1)[C]
• Immunosuppressive therapy (antithymocyte globulin [ATG] and cyclosporine) if no suitable donor
Diet
No special diet, but nutritious diet is important to improve resistance to infection.
Activity
Isolation procedures if neutropenic in addition to prophylactic antibiotic and antifungal
Nursing
If neutropenic, use antiseptic mouthwash such as chlorhexidine and give food low in bacterial content.
MEDICATION (DRUGS)
• Antithymocyte globulin (ATG):
- A horse serum containing polyclonal antibodies against human T cells. Skin test patients to determine any hypersensitivity.
- Treatment for patients >40 and patient without a compatible donor. Consider in patients 30-40.
- May be used as a single agent or in combination with cyclosporine. Increased efficacy with combination for children and patients with absolute neutropenia.
• Cyclosporine following initial ATG therapy for minimum of 6 months
- Monitor through blood levels. Normal values for assays vary.
- A 3-6 month trial may be necessary.
• Androgens
- Clinical trials are inconclusive.
- Useful for some patients lacking other options and less severe patients
• Oxymetholone: 1-2 mg/kg/d PO
- A 2-3 month trial is usually necessary to assess the response.
• Prednisone for pure red cell anemia
• Note: Relapses may occur after the initial response to the immunosuppressive therapy if cyclosporine is discontinued too early.
SURGERY
• Bone marrow transplantation for patients with severe aplastic anemia and an HLA-identical donor, 30 years old. Consider in patients 30-40 in good general medical condition
- Bone marrow stem cells and not mobilized peripheral stem cells should be used (B)
• Patients >40 have higher rates of graft versus host disease and graft rejection compared with children. Conditioning regimens are also poorly tolerated by older patients
• Unrelated donor transplants, if other therapy fails and/or 16 without HLA-matched sibling.
• Thymectomy for thymoma
FOLLOW-UP
PROGNOSIS
• Bone marrow transplantation with HLA-matched sibling: Long-term survival 75-80%
• Immunosuppressive therapy using ATG and cyclosporin: Overall survival of 75%; 90% among responders at 5 years.
COMPLICATIONS
• Infection(fungal, sepsis)
• Graft versus host disease in bone marrow transplant recipients (acute 18% chronic 26%)
• Side effects of immunosuppressant medications
• Hemorrhage
• Transfusion hemosiderosis
• Transfusion hepatitis
• Heart failure
• Development of leukemia or myelodysplasia (15-19% risk at 6-10 years
• Refractory pancytopenia
PATIENT MONITORING
Close monitoring for all treatments is recommended. Drugs and other forms of treatment have numerous and severe side effects.
REFERENCES
1. Marsh Ball, et al. Guidelines for diagnosis and treatment of acquired aplastic anemia. Br J Haematol. 2003;123(5):782-801.
2. Young, Abkowitz, Luzzatto. New insights into the pathophysiology of acquired aplastic anemia. Hematology. 2000;18-38.
3. Young NS. Acquired aplastic anemia. Ann Intern Med. 2002;136(7):534-546.

ANAPHYLAXIS

2008-12-31T01:15:00.000-08:00

ANAPHYLAXIS - BobbyPeters, MD, FAAEM
BASICS
DESCRIPTION
• An IgE mediated acute, systemic reaction following antigen exposure in a sensitized person
• A non-IgE mediated idiopathic anaphylactoid reaction also may occur. Anaphylactoid reactions are clinically indistinguishable from anaphylaxis and are treated in the same manner.
• System(s) Affected: Cardiovascular; Endocrine/Metabolic; Gastrointestinal; Hematologic/Lymphatic/Immunologic; Pulmonary; and Skin/Exocrine
• Synonym(s): Anaphylactoid reactions
GENERAL PREVENTION
• Avoid inducing drugs and foods.
• Carry a prefilled epinephrine syringe.
• Avoid areas where insect exposure likely. Avoid wearing insect attractants (e.g., perfumes, colored clothing); avoid bare feet outdoors.
• Carry or wear a medical alert ID about the anaphylaxis-causing substance or event.
• When radiologic contrast is unavoidable, use of low osmolar contrast agents (e.g., iothalamate) reduces the risk of contrast reactions to 3.1%.
- Only 0.22% were considered severe.
- Stop beta-blockers before administering contrast materials.
- Pretreat with diphenhydramine (50 mg IV) and a steroid (e.g., methylprednisolone 60 mg IV q6h until procedure). Start methylprednisolone the day before the procedure is scheduled.
• Those with frequent (>6 per year) episodes of idiopathic anaphylaxis should be treated prophylactically with prednisone (40-60 mg/d in a single morning dose), hydroxyzine (25 mg t.i.d.), and albuterol (2 mg PO t.i.d.). The prednisone should be rapidly tapered to a every other day regimen.
ALERT
• Have a latex-free kit (gloves, etc) available for the treatment of latex-allergic patients. Some latex-allergic patients will react to tropical fruits, such as kiwi, bananas, avocados, and chestnuts.
• Avoid beta-blockers.
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
• Up to 40,000 cases of idiopathic anaphylaxis occur per year with no identifiable cause.
• Drug-induced anaphylaxis in 1/2,700 hospitalized patients
• Anaphylaxis deaths: 0.3-0.7/100,000 per year
RISK FACTORS
• Previous anaphylaxis
• History of atopy or asthma
Genetics
Genetic predisposition for sensitization to antigens.
ETIOLOGY
• IgE-mediated mast cell degranulation
• Complement activation (C3a, C4a, C5a) by antigen-antibody complexes that contain complement-fixing antibodies.
• Other non-IgE-dependent anaphylaxis-like syndromes may be caused by modulators of arachidonic acid metabolism, sulfiting agents, exercise-induced anaphylaxis, and idiopathic recurrent anaphylaxis.
• Some important causes of anaphylaxis are:
- Antimicrobials (e.g., penicillin)
- Blood products (especially in IgA deficiency)
- Iodinated contrast media
- Ethylene oxide gas (dialysis tubing, other sterilized products)
- Exercise
- Foods (Common: Peanuts, nuts, fish, crustaceans, mollusks, cow milk, eggs, and soy)
- Immunotherapy
- Insect stings (e.g., honeybees, wasps, kissing bugs, and deer flies)
- Latex rubber (gloves, catheters)
- Macromolecules (e.g., chymopapain, insulin, dextran, glucocorticoid, and protamine)
- Vaccines
ASSOCIATED CONDITIONS
• Asthma
• Atopy

DIAGNOSIS
SIGNS AND SYMPTOMS
Physical Exam
• Pruritus, flushing, urticaria, angioedema
• Dyspnea, cough, rhonchi
• Rhinorrhea, bronchorrhea, wheezing
• Difficulty swallowing
• Nausea, vomiting, diarrhea, cramps, bloating
• Tachycardia, hypotension, shock, syncope
• Malaise, shivering
• Mydriasis
TESTS
Lab
• Hypoxemia, hypercarbia, acidosis
• Acidosis may cause apparent hyperkalemia by moving potassium extracellularly.
• Elevated serum tryptase, a mast cell enzyme for allergic and anaphylactic reactions. (11)[B]
• Drugs that may alter lab results: Epinephrine and albuterol may cause apparent hypokalemia by shifting K+ intracellularly.
DIFFERENTIAL DIAGNOSIS
• Anaphylactoid reactions
- May occur after the 1st contact with substance, such as polymyxin, pentamidine, radiographic contrast media, and aspirin.
• Carcinoid syndrome
• Globus hystericus
- May mimic pharyngeal edema
• Hereditary angioedema
- C1q esterase deficiency with painless, pruritus-free angioedema without urticaria, flushing, or wheezing
• Pheochromocytoma
- Paradoxically, because of beta-2 stimulation, some patients have hypotensive attacks accompanied by tachycardia.
- Urticaria, angioedema, and wheezing are absent
• Pseudoanaphylactic reaction
- After injection of procaine penicillin
- Is a drug effect of procaine and not a penicillin allergy
• Scombroid poisoning
- From ingestion of dark meat fish (e.g., tuna, mackerel, and mahi-mahi)
- Histamine-like mediator: Symptoms include flushing, sweating, nausea, vomiting, diarrhea, headache, palpitations, dizziness, rash, swelling of face and tongue, respiratory distress, and vasodilatory shock.
• Serum sickness
- Occurs several days after exposure
• Systemic mastocytosis
- Benign or malignant overgrowth of mast cells
- Urticaria pigmentosa seen in the benign form and the presence of reddish brown macular-papular cutaneous lesions, which urticate after trauma: Darier's sign.
• Vasovagal reactions
- Bradycardia and hypotension without tachycardia, flushing, urticaria, angioedema, pruritus, and wheezing
• Pulmonary embolism, foreign body aspiration, and arrhythmia
TREATMENT
GENERAL MEASURES
• Treatment depends on severity
• Maintain a patent airway
- Endotracheal intubation and assisted ventilation may be necessary.
- Possibly tracheostomy or needle cricothyrotomy in children 12 years
• Oxygen
• IV fluids (normal saline/lactated ringers)
Diet
Nothing until acute symptoms are controlled.
Activity
Bedrest until anaphylaxis clears and patient hemodynamically stable.
MEDICATION (DRUGS)
First Line
• Epinephrine
- Less severe reaction: 0.3-0.5 mg (0.01 mg/kg in children) = (0.3-0.5 mL of a 1:1,000 solution, 0.01 mL/kg in children), SQ q20-30min as needed up to 3 doses
- Life-threatening reactions: 0.5 mg (5 mL of a 1:10,000 solution) (for children: 0.05-0.1 mL/kg per dose) given IV slowly q5-10min as needed. If IV access is not possible, endotracheal or intraosseous may be effective.
• Diphenhydramine, an H1 blocker: 25-50 mg intravenously (IM or PO:) q6h for 72 hours (children 1.25 mg/kg to 25 mg)
• Cimetidine, an H2 blocker: 300 mg IV over 3-5 minutes (children 5-10 mg/kg per dose) and then 400 mg PO. b.i.d. is helpful and may be more effective than diphenhydramine.
• Corticosteroids: No immediate effect and unclear if they prevent recurrence.
- Hydrocortisone sodium succinate: 250-500 mg IV q4-6h (4-8 mg/kg for children) or
- Prednisone: 1 mg/kg in children, up to 60 mg
- Methylprednisolone: 60-125 mg IV in adults (1-2 mg/kg in children)
• Bronchodilator, if persistent bronchospasm
- Inhaled beta-2 agonists. Continuous nebulized albuterol of 10 mg per hour or 2.5 mg q15-20 min is safe, effective, and preferable to aminophylline as a first line.
• Laryngeal edema:
- Epinephrine: 5 mL 1:1,000 by nebulizer is more effective than racemic epinephrine and usually available.
• Persistent hypotension
- Dopamine: 200 mg in 500 mL of dextrose in water given by infusion pump; titrate to BP (3-20 mcg/ kg per minute)
- Glucagon: May be beneficial for resistant hypotension caused by concurrent beta-blockade therapy; 50 mcg/kg IV bolus over 1 minute, or alternatively, give as continuous infusion at 5-15 mcg/min
• Normal saline or Ringer's lactate: As necessary to maintain tissue perfusion
• Oral antihistamines and steroids for 72 hours
ALERT
Geriatric Considerations
Epinephrine may induce myocardial ischemia in those with cardiac disease, but is the drug of choice. Be alert for anticholinergic and CNS side effects after giving diphenhydramine or cimetidine.
Pediatric Considerations
Epinephrine could reduce the placental blood flow, but may save the life of the mother and fetus. It also increases risk of congenital malformation.
Second Line
• Several reports of tranexamic acid: 1,000 mg IV or sigma-aminocaproic acid for refractory anaphylaxis
• These drugs are not standard care; use only in patients who do not respond to other therapy.
• Aminophylline: 5-6 mg/kg IV in 100 cc D5W over 20 minutes, then maintenance at 1 mg/kg/h drip
• Anti-IgE monoclonal antibody may have a role in long-term management of food-induced anaphylaxis. (12)[B]
• Venom immunotherapy has been effective in the prevention of sting anaphylaxis, but with a high side-effect risk. (13)[A]
FOLLOW-UP
DISPOSITION
Admission Criteria
Moderate-severe anaphylaxis, admit for observation
Discharge Criteria
Outpatient: Patients with cutaneous angioedema, urticaria, and minimal bronchospasm may be released when symptoms and signs have cleared.
Issues for Referral
• Allergist referral, if anaphylaxis cause unclear
• Patients with anaphylaxis from insect stings benefit from desensitization immunotherapy.
PROGNOSIS
• Good prognosis if treated immediately; worse outcome with a delay of >30 minutes in administration of epinephrine
• Of those with idiopathic anaphylaxis, 60% are free of anaphylactic episodes at 2.5 years; most others were steroid-free
COMPLICATIONS
• Hypoxemia
• Cardiac arrest
• Death
REFERENCES
1. Anne S, et al. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol.1995;74:167.
2. The Diagnosis and Management of Anaphylaxis. Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy. Asthma and Immunology. Allergy 1998;6.
3. Freeman TM. Allergy and Immunology. Anaphylaxis: Diagnosis and treatment. Prim Care. 1998;25:809.
4. Hoste S, Van Aken, Stevens E. Tranexamic acid in the treatment of anaphylactic shock. Acta Anaesthesiologica Belgica. 1991;42:113-116.
5. Patterson R, Hogan B, Yarnold PR, Harris KE. Idiopathic anaphylaxis: An attempt to estimate the incidence in the United States. Arch Int ed. 1995;155:869-871.
6. Sandler SG, Mallory, Malamut D, Eckrich R. IgA anaphylactic transfusion reactions. Transfus Med Rev. 1995;9:1-8.
7. Sloop GD, Friedberg C. Complications of blood transfusion: how to recognize and respond to noninfectious reactions. Postgrad Med. 1995;98:159-162,166,169-172.
8. Tanus T, Mines D, Atkins PC, Levinson AL. Serum tryptase in idiopathic anaphylaxis: A case report and review of the literature. Ann Emerg Med. 1994;24:104-107.
9. Tintinalli JE, et al. Emergency Medicine, A Comprehensive Study Guide. 4th ed. New York, NY: McGraw-Hill; 1995.
10. Wittbrodt ET, Spinler A. Prevention of anaphylactoid reactions in high-risk patients receiving radiographic contrast media. Ann Pharmacother. 994;28:236-241.
11. Brown SG, Blackman KE, Heddle RJ. Can serum mast cell tryptase help diagnose anaphylaxis? EMA. 16;2:120-124.
12. Leung DY, Shanahan WR, Li XM, Sampson HA. New approaches for the treatment of anaphylaxis. Novartis Foundation Symposium. 257:248-260.
13. Brown SG, Wiese MD, Blackman KE, Heddle RJ. Ant venom immunotherapy: A double-blind, placebo-controlled, crossover trial. Lancet. 361;9362:1001-1006.

ANAL FISSURE

2008-12-31T01:13:00.000-08:00

ANAL FISSURE - MichaelRousse, MD, MPH
BASICS
DESCRIPTION
Anal fissure is a benign ano-rectal disease characterized by a knife-like tearing sensation upon defecation. An anal fissure is a tear in the lining of the anal canal distal to the dentate line, most commonly in the posterior midline.
GENERAL PREVENTION
Avoid local trauma or stretch of the anal canal. Soften stool by maintaining adequate hydration and fiber intake.
EPIDEMIOLOGY
• Very common ano-rectal condition. Often confused with hemorrhoids by lay person and primary care physicians.
• Predominant age: Early adult. Elderly are spared this affliction due to lower resting pressure in the anal canal.
• Predominant sex: Affects men and women equally but women more likely to get anterior midline tears (25% vs 8%). Any tear off of the midline, suspect a secondary cause.
Incidence
Exact incidence is unknown. Patients often treat with OTC and home remedies and do not seek the advice of a physician.
Prevalence
As many as 20% of patients, the majority of whom did not seek the advice of a physician, have symptoms referable to the ano-rectum.
ALERT
Geriatric Considerations
Less common in the elderly because of lower resting anal sphincter tone
Pediatric Considerations
Not common in children, suspect abuse/trauma
RISK FACTORS
Constipation, passage of hard stool, high resting tone of internal anal sphincter, trauma, Crohn disease, HIV, syphilis, and TB
Pregnancy Considerations
Possible in pregnancy due to constipation and increased rectal pressure during and after pregnancy
Genetics
None known
PATHOPHYSIOLOGY
High resting pressure within the anal canal can lead to ischemia of the ano-dermal tissues; this increases the likelihood of splitting of the tissue with passage of stool. Thereafter, spasm of the internal anal sphincter results with or without passage of stool causing extreme, "knife-like," pain.
ETIOLOGY
Stretching and splitting of susceptible ano-dermal tissue
ASSOCIATED CONDITIONS
Crohn disease, TB, leukemia, and HIV

DIAGNOSIS
PRE HOSPITAL
ALERT
Special Considerations
Knife-like pain with defecation, associated blood streaked bowel movement
SIGNS AND SYMPTOMS
Patients present with severe rectal pain, often with and following defecation, pain may be continuous. They may describe bright red blood on stool or streaking the paper when wiping. Occasional itch or perianal irritation.
History
Pain and bleeding with defecation
Physical Exam
Gentle spreading of the buttocks will reveal a tear in the ano-dermal tissue, typically posterior midline, occasionally anterior midline, rarely eccentric to midline. Minimal swelling or bleeding. Hypertrophic papillae/sentinel tag seen in chronic fissure.
Diagnostic Procedures/Surgery
None, avoid anoscopy or endoscopy
• Some cases may require exam under anesthesia.
Pathological Findings
Tear in ano-derm, hypertrophic papillae, and sentinel tag.
DIFFERENTIAL DIAGNOSIS
• Thrombosed external hemorrhoidabsence of swollen mass
• Peri-rectal abscessfissure rather than a sinus
• SyphilisRare cause of recurrent fissures
TREATMENT
GENERAL MEASURES
Stool softeners, analgesics, and anxiolytics
Diet
High fiber, extra fluids
Activity
No restrictions
Nursing
No restrictions
SPECIAL THERAPY
Sitz baths
MEDICATION (DRUGS)
Directed at reducing muscle spasm within the internal anal sphincter, softening stool to facilitate atraumatic passage, and pain relief. (1)[C]
First Line
• Stool softeners, fiber supplementation
• Analgesics
• Nitratestopical nitroglycerin ointment 2% applied q.i.d.
Second Line
• Botulinum toxin4 mL injected into the internal sphincter muscle
• Calcium channel blockersoral or topical
SURGERY
• Reserved for failure of medical therapy, involves division of the internal sphincter muscle via various surgical approaches.
• Risk of fecal incontinence 45% in the short term, 6-8% in the long term. (2)[C]
FOLLOW-UP
DISPOSITION
Issues for Referral
Medical therapy usually tried for 90 days, surgery is then considered
PROGNOSIS
Topical therapy is less likely to be successful for chronic fissures, ~40% failure rate. (2)[C]
COMPLICATIONS
Fecal incontinence and incontinence to flatus are primarily associated with surgery.
PATIENT MONITORING
• Once healed, most patients should have a colonoscopy to further work-up rectal bleeding.
• If 50, sigmoidoscopy may be sufficient.
REFERENCES
1. MacLeod J. A Method of Proctology. New York: Harper  Row,
2. Breen E, Bleday R. Anal Fissure, Up To Date, 13.3. Waltham, 2006.
3. Schwartz S. Principles of Surgery, 7th ed. New York,McGraw-Hill;1999;1298-1299.

ANAEROBIC AND NECROTIZING INFECTIONS

2008-12-31T01:11:00.000-08:00

ANAEROBIC AND NECROTIZING INFECTIONS - Ruben Peralta, MD, FACS; Hongyi Cui, MD, PhD
BASICS
DESCRIPTION
• Necrotizing infection of the skin and fascia are called necrotizing cellulitis and necrotizing fasciitis respectively.
• Anaerobic and necrotizing infections may be associated with gas in tissue.
• Necrotizing fasciitis is a rapidly spreading and potentially fatal soft-tissue infection located in the deep fascia, with secondary necrosis of the subcutaneous tissue. Organisms spread from the subcutaneous tissue along the deep fascial planes, presumably facilitated by bacterial enzymes and toxins.
• Type I necrotizing fasciitis is a mixed infection caused by the synergistic effect of both aerobic and anaerobic bacteria; Type II necrotizing fasciitis refers to a monomicrobial infection caused by group A -hemolytic streptococcus (GAS).
• Gas gangrene is a subset of necrotizing myositis usually caused by the Clostridium species with gas formation within the tissue.
• Necrotizing skin and soft-tissue infection is usually associated with extensive destruction of tissue, systemic toxicity, loss of limb, and even death.
ALERT
Geriatric Considerations
Increased risk with age >60
GENERAL PREVENTION
• Avoidance of trauma
• Good care of skin
• Control of diabetes
• Avoidance of tight orthopedic casts
• Follow routine surgical principles for skin closure
EPIDEMIOLOGY
• Predominant age: Any age
• Predominant sex: Male = Female
Incidence
Incidence of necrotizing faciitis 1,000-1,500 cases annually in the US
Prevalence
Rare
RISK FACTORS
• Tissue poor blood supply
• Old age
• Trauma
• Diabetes mellitus
• Malnutrition
• Immune suppression (e.g., HIV, malignancies, steroid use, etc.)
• Chickenpox
• Cigarette smoking
• Alcoholism
• Obesity
• Intravenous drug abuse
• Surgery
ETIOLOGY
Necrotizing fasciitis often begins as a cutaneous injury, which could be minor; a necrotizing process then begins below the dermis and spreads radially.
ASSOCIATED CONDITIONS
See "Risk Factors."

DIAGNOSIS
SIGNS AND SYMPTOMS
• Most important symptom is pain out of proportion to exam
• Malaise, anorexia
History
Most common predisposing conditions: Most cases arise from previous trauma or infection (surgical wound from open or laparoscopic procedure, ulcers, burns, IV drug injection site, abscess). May develop without apparent cause.
Physical Exam
The diagnosis of necrotizing fasciitis is clinical, based on physical exam
• Localized erythema and edema
• Skin discoloration with vesicle formation
• Foul odor
• Fever, often low grade early in the disease
• Tachycardia, hypotension
• Diaphoresis
• Rapidly spreading skin lesion
TESTS
Lab
• No test result is diagnostic, except frozen section biopsy of the fascia. Treatment should not be delayed while awaiting biopsy. Diagnosis is made clinically.
• Cultures and sensitivity tests for microorganisms reported to produce gas in human tissues
- Gram-positive anaerobes
 Cocci: Peptostreptococcus (anaerobic Streptococcus) (usually with group A streptococci [Streptococcus pyogenes, beta-hemolytic streptococci] or Staphylococcus aureus)
 Bacilli: Clostridium perfringens and other clostridia
- Gram-negative aerobes: Bacilli: Escherichia coli, Klebsiella pneumoniae, Enterobacter species, Proteus species (all usually in mixed infections)
- Gram-negative anaerobes: Bacilli: Bacteroides fragilis (usually with other gram-negative bacilli)
• With severe gangrene, studies will reveal anemia and leukocytosis.
• Gram smears for many possible organisms
• Daily serum creatine kinase
• Elevated liver functions may result from release of bacterial toxins.
• Renal dysfunction may occur secondary to hypotension and myoglobinuria.
• Drugs that may alter lab results
- Antibiotics before culture
Imaging
• Plain radiographs
- Gas in tissues; foreign body if present
• CT
- Soft-tissue swelling and presence of gas in tissues
Diagnostic Procedures/Surgery
Immediate surgical intervention, with longitudinal incisions of skin, superficial fascia, deep fascia, and muscles to look for and remove necrotic tissue and/or foreign bodies
• Multiple daily surgical interventions may be required.
Pathological Findings
Soft-tissue necrosis, with polymorphonuclear cells and vascular thrombosis
DIFFERENTIAL DIAGNOSIS
Other soft-tissue infection including abscess and post-surgical wound infection
TREATMENT
GENERAL MEASURES
• Infectious disease consultation, if available
• IV fluids with electrolyte repletion, if indicated
• Daily complete blood count and electrolytes in acute phase
• Prophylaxis for tetanus
• Hyperbaric oxygen in selected cases
Diet
By mouth, as tolerated
Activity
Bed rest
SPECIAL THERAPY
Hyperbaric oxygen
• Unclear therapeutic value
• No delay of surgical intervention for hyperbaric oxygen therapy
MEDICATION (DRUGS)
• Initially broad-spectrum antibiotic regimen, then tailor to organisms identified by blood and wound cultures and organism sensitivities. (1)[B]
• Initial broad spectrum coverage should include penicillin, which will provide coverage of Streptococcus, and clindamycin, which works synergistically with penicillin when large bacterial load is present and also binds Group A Steptococcus toxin.
• Aminoglycosides will cover enteric Gram-negative organisms.
• Metronidazole is an alternative to clindamycin for treatment of anaerobic organisms.
• For vibrio species, tetracycline can be used.
• Retrospective studies suggest there may be a survival benefit with the use of Intravenous Immunoglobulin (IVIG) therapy. IVIG works by binding toxins and binds superantigens which suppresses pro-inflammatory mediators. (2)[B]
• Important: Do not delay treatment even if smear, cultures, and tests are negative.
• Unlike Clostridia perfingens and group A -hemolytic streptococci, the Aeromonas species are uniformly resistant to penicillin-G but are reported highly sensitive to 3rd-generation cephalosporins.
• Precautions: Delay of operative treatment is an important determinant of increased morbidity and mortality.
SURGERY
• Necrotizing soft tissue infections are a surgical emergency. Patients should be taken to the operating room once the diagnosis is made.
• All necrotic tissue should be resected. Dissection should be carried along all involved fascial planes. Preservation of tissue should not take precedence over adequate debridement.
• If a limb is involved, amputation might be necessary because of extensive fascial and subcutaneous soft tissue necrosis and overwhelming systemic toxicity.
• Adequate surgical treatment can rarely be accomplished with a single operation. Debridement should continue until all necrotic tissue is removed. Multiple debridements is the norm.
• Negative pressure suction dressing (i.e., VAC dressing) may be utilized to improve wound care and assist with postoperative fluid management.
• Wound coverage and reconstruction can be undertaken once systemic sepsis has been controlled, all nonviable tissue has been removed and local bacterial control in the wound has been achieved.
FOLLOW-UP
DISPOSITION
• Following surgical debridement, patients should be monitored and managed in an ICU setting if clinically indicated.
• Close contacts of patients and health care workers do not require chemoprophylaxis with antibiotics. (3)[B]
PROGNOSIS
• Mortality for necrotizing fasciitis decreased to 14% in 2002 from nearly 28% in 1994. (4)[B]
• Risk factors for mortality are associated with the following: Pre-existing and concurrent health conditions age >60 years, male, malnutrition, IV drug abuse, bacteremia, history of pulmonary or heart disease or carcinoma.
COMPLICATIONS
• Tissue and functional losses
• Amputation
• Fulminant course leading to death without treatment
PATIENT MONITORING
• As clinically indicated; may include following cultures, electrolytes, drug levels
• May require surgical critical care management in an ICU.
• Diligence required to recognize spreading gangrene
REFERENCES
1. Elliott D, Kufera JA, Myers RA. The microbiology of necrotizing soft tissue infections. Am J Surg 2000;361-366.
2. Norrby-Telund A, Low DE. Group A Streptococcal Toxic Syndrome and Necrotizing Fasciitis. Current Treatment Options in Infectious Diseases 2003;5,419-429.
3. Smith A. Invasive group A streptococcal disease: Should close contacts routinely receive antibiotic prophylaxis? Lancet Inf Dis 2005;5:494-500.
4. MMWR, 2005 51(53) 11 and MMWR 1994;43:401.

AMYOTROPHIC LATERAL SCLEROSIS

2008-12-31T01:09:00.000-08:00

AMYOTROPHIC LATERAL SCLEROSIS - Colin R.Bamford,MD
BASICS
DESCRIPTION
A degenerative disease (or group of diseases), that affects the upper and lower motor neurons
• Amyotrophic lateral sclerosis is the term applied to the sporadic and most common form of the disease. It includes a number of overlapping syndromes, such as pseudobulbar palsy, progressive bulbar palsy, progressive muscular atrophy, and primary lateral sclerosis.
• Familial ALS is an autosomal dominant or recessive disease, which is clinically similar to sporadic ALS but probably represents a distinct entity pathologically and biochemically.
• ALS-Parkinson-dementia complex of Guam is an ALS-like syndrome, often, but not always, associated with Parkinson syndrome and dementia, which is prevalent among the Chamorro Indians of Guam and very rare in the United States.
• System(s) Affected: Nervous
• Synonym(s): Motor neuron disease; Lou Gehrig disease; ALS
ALERT
Pediatric Considerations
• Infantile and juvenile spinal muscular atrophies are conditions that are distinct from amyotrophic lateral sclerosis both clinically and pathologically.
• Symptoms of ALS may inappropriately be attributed to age.
Pregnancy Considerations
• Uncommon among affected individuals
• Pregnancy would be unwise in any individual suffering from a disease with so poor a prognosis.
• If pregnancy did occur, the only foreseeable difficulties would be related to weakness.
EPIDEMIOLOGY
Incidence
0.4-2.0/100,000
Prevalence
• 5.0-8.0/100,000
• Predominant age: Uncommon before age 40
• Predominant sex: Male > Female
RISK FACTORS
Age > 40
Genetics
Familial ALS
ETIOLOGY
• Sporadic ALS: Degeneration of the upper and lower motor neurons with their respective axons
- Cause is unknown, but elevated levels of glutamate have been found in serum and cerebrospiral fluid (CSF)
- High levels of glutamate are toxic; 90-95% of the cases of ALS are sporadic.
• Familial ALS: A genetically transmitted degenerative disease
- Gene locus has been localized to the long arm of chromosome 21 and encodes the enzyme superoxide dismutase in 20% of familial ALS cases. 5-10% of the ALS cases are familial.
• ALS-Parkinson-dementia complex of Guam: Possible relationship to ingestion of the cycad nut or to some other environmental toxin

DIAGNOSIS
SIGNS AND SYMPTOMS
Physical Exam
Variable combinations of
• Unexplained weight loss
• Focal wasting of muscle groups
• Limb weakness with variable symmetry and distribution
• Difficulty walking
• Difficulty swallowing
• Slurring of speech
• Inability to control affect
• Atrophy of muscle groups, initially in a myotomal distribution
• Fasciculations (other than calves)
• Hyperactive deep tendon reflexes (including jaw jerk)
• Spares cognitive, oculomotor, sensory, and autonomic functions
TESTS
Lab
• Elevated levels of glutamate in CSF and serum
• Anti-monosialoganglioside autoantibodies in low titer commonly found (of unclear significance)
• Possibly reduced levels of nerve growth factor
• There is no simple reliable laboratory test available that confirms the diagnosis of ALS.
Diagnostic Procedures/Surgery
• Electromyography: Denervation potentials (fibrillations, positive sharp waves) and often doublets are associated with prominent fasciculations, which suggest anterior horn cell dysfunction. Voluntary motor unit potentials have increased amplitude, long duration, and/or polyphasic pattern. The recruitment pattern is reduced for the force generated, and individual motor units have a high rate of discharge.
• Muscle biopsy: The biopsy will show groups of shrunken angulated muscle fibers (grouped atrophy) amid other groups of fibers with a uniform fiber type (fiber type grouping).
Pathological Findings
• Loss of Betz cells in the motor cortex
• Atrophic or absent anterior horn cells of spinal cord
• Atrophic or absent neurons within the motor nuclei of the medulla and pons
• Degeneration of the lateral columns of the spinal cord
• Atrophy of the ventral roots
• Grouped atrophy of muscle (motor units)
DIFFERENTIAL DIAGNOSIS
• Focal motor neuropathy
• Cervical spondylosis
• Lead intoxication
• Spinal muscular atrophy (adult form)
• Primary lateral sclerosis
• Familial spastic paraparesis
• Spinal multiple sclerosis
• Tropical spastic paraparesis
TREATMENT
GENERAL MEASURES
• Outpatient initially, may ultimately need nursing home placement and/or hospice
• Supportive care is necessary for complicating emergencies (aspiration, respiratory failure). Use of a respirator is a major ethical dilemma. Consideration should be given to those with selective respiratory dysfunction.
• Discussion of advance directive, focusing on patient's specific values about which interventions to be used, is critical to meeting the patients needs.
• Prosthetic devices (e.g., wheelchair)
Diet
Modify as tolerated; tube feedings may be necessary
Activity
As tolerated
SPECIAL THERAPY
Therapeutic trials of the efficacy of antioxidants (vitamins E and C and beta-carotene), nerve growth factor, gabapentin, myotrophin, and thyrotropin-releasing hormone have been undertaken. Reports are not encouraging.
MEDICATION (DRUGS)
Riluzole produces a slight prolongation in life expectancy by decreasing the release of glutamate.
FOLLOW-UP
PROGNOSIS
• ALS usually results in death within 5 years.
• Patients who predominantly manifest progressive muscular atrophy have a better prognosis.
• There have been reports of spontaneous arrest of the disease.
COMPLICATIONS
• Aspiration pneumonia
• Decubitus ulcers
• Pulmonary embolism
• Nutritional deficiency
PATIENT MONITORING
• Initially every 3 months, frequency to be increased as needed for symptomatic therapy
• Patients with a presumed diagnosis of ALS should have imaging of the cervical spine and electrodiagnostic studies.
REFERENCES
1. Brown WF, Botton CF. Clinical Electromyography. 2nd ed. Boston, MA: Butterworth-Heinemann; 1993.
2. Rowland LD, ed. Merritt's Textbook of Neurology. 9th ed. Philadelphia, PA: Williams  Wilkins; 1995.
MISCELLANEOUS
Also referred to as Mill's variant (unilateral involvement)

AMYLOIDOSIS

2008-12-31T01:07:00.000-08:00

AMYLOIDOSIS - Karin S. Leschly, MD
BASICS
DESCRIPTION
• A group of diseases characterized by increased deposition of amyloid fibrils in the tissues. Several different proteins may give rise to amyloid.
• These proteins are present due to their overproduction or decreased clearance. Their deposition may lead to compromise of vital organ function.
• Specific amyloid proteins aggregate mostly in specific organs.
• Primary or idiopathic (AL form): No associated disease
• Secondary, acquired, or reactive (AA form): Associated with chronic diseases, either infectious (tuberculosis, bronchiectasis, osteomyelitis, leprosy) or inflammatory (rheumatoid arthritis, granulomatous ileitis); Hodgkin disease; other tumors; and familial Mediterranean fever.
• Familial (hereditary) amyloidosis: Associated with distinctive types of neuropathy, nephropathy, and cardiopathy; may occur in almost every ethnic group
• Hemodialysis amyloidosis: Associated with renal hemodialysis
• Localized amyloidosis: Associated with Alzheimer disease
• System(s) affected: Cardiovascular; Endocrine/metabolic; Gastrointestinal; Musculoskeletal; Nervous; Pulmonary; Renal/urologic; Skin/exocrine
ALERT
Geriatric Considerations
• In general, older individuals do less well.
• Age may precipitate familial amyloidosis, suggesting an age-related trigger.
EPIDEMIOLOGY
Incidence
• Primary amyloidosis: 1 per 100,000 person-years
• Secondary amyloidosis: Very rare
• Familial amyloidosis: 1 per million person-years
Prevalence
• Predominant age: 60-70
• Predominant sex: Male > Female (2:1)
RISK FACTORS
• Underlying plasma cell dyscrasia
• Underlying chronic inflammatory disease
• Familial Mediterranean fever
• Hemodialysis
Genetics
Only familial amyloidosis can be inherited. The genetics are variable but usually are autosomal dominant.
ETIOLOGY
• The cause of amyloid production and its deposition in tissues is unknown.
• In the different types of amyloidosis, etiologic mechanisms may vary. For example
- Primary amyloidosis: The amyloid consists of immunoglobulin light chains, which are overproduced in plasma-cell disorders.
- Secondary amyloidosis: The amyloid consists of amyloid fibrillary protein formed from serum amyloid protein, which is overproduced in chronic inflammatory conditions.
- Familial (hereditary) amyloidosis: The amyloid consists of abnormal transthyretin protein or lysozyme protein produced in the liver.
- Hemodialysis amyloidosis: The amyloid consists of 2-microglobulin, which is normally cleared by the kidney, but not by hemodialysis.
- Localized amyloidosis: Associated with hormonal proteins or aging, such as -amyloid proteins in Alzheimer disease and other neurodegenerative diseases
ASSOCIATED CONDITIONS
Amyloid may bind Factor X, leading to bleeding problems.

DIAGNOSIS
SIGNS AND SYMPTOMS
Manifestations are nonspecific, determined by the organ or system affected, and often are obscured by the underlying disease, which may be fatal before amyloidosis is suspected.
History
Fatigue, weight loss, gastroparesis, pseudo-obstruction, malabsorption, diarrhea, macroglossia
Physical Exam
• Nephrotic syndrome is the most striking manifestation: Early stages, slight proteinuria; late stages, anasarca, hypoproteinemia, and massive proteinuria
• Hepatic amyloid disease produces hepatomegaly, but rarely jaundice. Occasionally portal hypertension may occur, with esophageal varices and ascites.
• Cardiac involvement is common and may present as cardiomegaly, intractable heart failure, or any common arrhythmia.
• GI amyloid may cause esophageal motility abnormalities, gastric atony, small- and large-intestinal motility abnormalities, gastric atony, small- and large-intestinal motility abnormalities, malabsorption, bleeding, or pseudo-obstruction.
• Peripheral neuropathy, carpal tunnel syndrome
• Lung involvement may be characterized by focal pulmonary nodules, tracheobronchial lesions, or diffuse alveolar deposits. Patients may present with dyspnea, congestive heart failure, arrhythmia, angina pectoris, or sudden death
• Hilar adenopathy, mediastinal adenopathy
• Amyloid arthropathy may mimic rheumatoid arthritis: Symmetrical polyarthritis, rubbery periarticular soft-tissue swelling
• Skin lesions may be translucent or waxy; purpura (periorbital purpura) may result from amyloidosis of small cutaneous vessels, edema
• Dementia (may have role in Alzheimer disease)
• Macroglossia is common in primary and myeloma-related amyloidosis.
• A firm, symmetric, nontender goiter resembling Hashimoto or Riedel struma may result from amyloidosis of the thyroid gland.
TESTS
Specialized screening for mutant transthyretin
Lab
• Anemia may be present.
• Hypothyroidism may be present due to amyloidosis of the thyroid.
• Renal insufficiency is present in 50%.
• Proteinuria is present in ~80%.
• Primary amyloidosis
- Elevated monoclonal protein level will be found in the serum and/or urine.
• Secondary amyloidosis
- Tests to assess the underlying inflammatory disease will be useful.
• Familial amyloidosis
- An abnormal transthyretin protein may be isolated.
Imaging
Echocardiography (if cardiac involvement is suspected)
Diagnostic Procedures/Surgery
• Amyloidosis is suspected on the basis of symptoms and signs, but can be diagnosed only by biopsy.
• Abdominal fat pad biopsy (up to 85% positive)
• Rectal biopsy (70% positive)
• Bone marrow biopsy (20% positive)
• Endomyocardial biopsy
• Renal biopsy
Pathological Findings
• Demonstration of amyloid deposits in tissues
• With Congo red staining, amyloid produces a green birefringence under polarized light.
• Electron microscopy is the definitive diagnostic tool.
DIFFERENTIAL DIAGNOSIS
• Peripheral neuropathy: Diabetes mellitus, alcoholism, vitamin deficiencies
• Carpal tunnel syndrome: Hypothyroidism, trauma, rheumatoid arthritis, late pregnancy
• Restrictive cardiomyopathy: Acute viral myocarditis, endomyocardial fibrosis, sarcoidosis, hemochromatosis
• Nephrotic syndrome: Glomerulonephritis, renal vein thrombosis
• Renal failure: Glomerulonephritis, obstructive uropathy, toxin- or drug-induced, acute tubular necrosis
• Symmetric polyarthritis: Rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus
• Interstitial lung disease: Connective tissue diseases, infectious, sarcoidosis, drug-induced, pneumoconiosis
• Dementia: Alzheimer disease, multi-infarct dementia, Parkinson disease
TREATMENT
GENERAL MEASURES
• Therapy is 1st directed to underlying cause; such treatment may arrest amyloidosis.
• Management is generally symptomatic.
• Appropriate health care: Outpatient, except for serious complications (CHF, renal failure)
• Hemodialysis amyloidosis: Change to peritoneal dialysis (clears 2-microglobulin).
Diet
• Low-protein, low-salt diet for renal failure patients
• Low-salt diet for CHF patients
Activity
• Fully active as tolerated
• Fatigue/shortness of breath may limit activity
MEDICATION (DRUGS)
• Primary amyloidosis
- Treatment of the underlying plasma-cell disorder may or may not affect the outcome.
- Melphalan and prednisone are among the drugs of choice for plasma-cell disorders.
- Thalidomide also effective
- The role of colchicine is considered less important; it may slow amyloid deposition.
• Secondary amyloidosis
- Treatment of the underlying inflammatory process with disease-specific medications usually improves the outcome (i.e., isoniazid and rifampin for M. tuberculosis, methotrexate for rheumatoid arthritis).
- Donepezil, galantamine, rivastigmine, and memantine have been approved for mild to moderate dementia caused by Alzheimer disease.
- Colchicine, 0.6 mg b.i.d.-t.i.d. may prevent acute attacks in familial Mediterranean fever.
• Familial amyloidosis: None
• Hemodialysis amyloidosis: None
• Precautions
- Melphalan: Bone marrow depression, including agranulocytosis, pancytopenia, thrombocytopenia, or aplastic anemia, may occur with prolonged administration. Monitor CBC periodically. Counsel patient to report symptoms/signs of infection (headache, sore throat, fever).
- Thalidomide: Severe birth defects
- Colchicine: Nausea, diarrhea, blood dyscrasia, rash, alopecia
SURGERY
• Splenectomy may ameliorate this condition by decreasing the amount of amyloid produced.
• Renal transplantation may improve the status of renal amyloidosis. However, amyloid will ultimately recur in a donor kidney.
• Liver transplantation or partial liver transplantation may cure familial (hereditary) amyloidosis.
• Other measures: Treatment of multiple myeloma with bone marrow transplantation is an option for some patients.
• A pacemaker may be indicated in those with amyloid-induced conduction defects.
FOLLOW-UP
PROGNOSIS
• Primary amyloidosis
- The prognosis depends on the underlying disease.
- Once renal failure has developed, the prognosis is usually 1 year.
- CHF has a 4-month prognosis.
- Overall prognosis is poor; reported survival rates are 51% at 1 year and 16% at 5 years.
• Secondary amyloidosis
- The prognosis is better, depending on ability to control the underlying process.
• Familial and hemodialysis amyloidosis
- Highly variable
- A liver transplant may be curative, but it is linked to the duration and severity of the pretransplant illness.
- The deposition of amyloid in the heart may continue even after successful transplantation.
COMPLICATIONS
Despite intervention, worsening renal failure, heart failure, arthropathy, interstitial lung disease, and neuropathy are common.
PATIENT MONITORING
• Primary amyloidosis
- Regular testing of monoclonal protein levels to assess response to therapy
- Regular testing of renal function to assess response to therapy
• Secondary and hemodialysis amyloidosis
- Follow-up to assess control of the underlying disease process
- Regular testing of renal function to assess degree of impairment
REFERENCES
1. Cohen AS, Rubinow A, Anderson JJ, et al. Survival of patients with primary (AL) amyloidosis. Colchicine-treated cases from 1976-1983 compared with cases seen in previous years (1 961-1973). Am J Med. 1987;82:1182-1190.
2. Dember L, Sanchorawala V, Seldin DC, et al. Effect of dose-intensive melphalan and autologous blood stem-cell transplantation on AL amyloidosis-associated renal disease. Ann Intern Med. 2001;134:746-753.
3. Fiter J, Nolla JM, Valverde J, et al. Methotrexate treatment of amyloidosis secondary to rheumatoid arthritis. Clin Rev of Spain. 1995;195:390-392.
4. Falk RH, et al. The systemic amyloidosis. N Engl J Med. 1997;337:898-909.
5. Kyle RA, Greipp PR, O'Fallon WM. Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases. Blood. 1986;68:220-224.
6. Kyle RA, Gertz MA, Greipp PR, et al. Long-term survival (10 years or more) in 30 patients with primary amyloidosis. Blood. 1999;93:1062-1066.
7. Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349:583-596.
8. Skinner M. Amyloidosis. In: Kelley WN, Harris ED, et al, eds. The Textbook of Rheumatology. Philadelphia: WB Saunders; 1996:1409-1417.

AMENORRHEA

2008-12-31T01:05:00.000-08:00

AMENORRHEA - Jeanne M. Cawse-Lucas, MD
BASICS
DESCRIPTION
The absence of menses.
• Primary amenorrhea: No menses by age 14, with absence of secondary sexual characteristics, or no menses by age 16 with normal secondary characteristics
• Secondary amenorrhea: The cessation of menses for 3 cycles, or 6 months of amenorrhea
• System(s) Affected: Endocrine/metabolic; Reproductive
ALERT
Pediatric Considerations
Primary amenorrhea by definition begins in this group.
Pregnancy Considerations
Pregnancy is the most common cause of secondary amenorrhea.
GENERAL PREVENTION
Maintenance of proper body mass index (BMI)
EPIDEMIOLOGY
Incidence
• Incidence of primary amenorrhea 0.3%
• Incidence of secondary amenorrhea 3.3%
Prevalence
Menarche to menopause
RISK FACTORS
• Overtraining (e.g., long-distance runner, ballet dancer) as part of the female athlete triad
• Eating disorders
• Psychosocial crisis
Genetics
No known genetic pattern
ETIOLOGY
• Primary amenorrhea
- Imperforate hymen
- Agenesis of the uterus and upper 2/3 of the vagina (Mullerian agenesis)
- Turner syndrome
- Constitutional delay
• Secondary amenorrhea
- Physiological: Pregnancy, corpus luteal cyst, breast-feeding, menopause
- Suppression of the hypothalamic-pituitary axis: Post-pill amenorrhea, stress, intercurrent illness, weight loss, and low BMI
- Pituitary disease: Ablation of the pituitary gland, Sheehan syndrome, prolactinoma
- Uncontrolled endocrinopathies: Diabetes, hypothyroidism, or hyperthyroidism
- Polycystic ovarian syndrome (PCOS), (Stein-Leventhal syndrome)
- Chemotherapy
- Pelvic irradiation
- Endometrial ablation (inducing Asherman syndrome)
- Drug therapy: Systemic steroids, danazol, GRH-RH analogs, antipsychotics, OCPs
- Premature ovarian failure
- Female athlete triad (amenorrhea, osteoporosis, and disordered eating habits)

DIAGNOSIS
SIGNS AND SYMPTOMS
History
The absence of periods
Physical Exam
• Galactorrhea
• Symptoms of hypothyroidism
• Symptoms of early pregnancy
• Signs of androgen excess
• Signs of estrogen deficiency
• Signs of congenital abnormalities such as imperforate hymen, absence of vagina or uterus
TESTS
• Progesterone challenge test: 10 mg of medroxyprogesterone acetate PO for 5 days: If withdrawal bleeding occurs, amenorrhea most likely due to chronic anovulation with estrogen (PCOS); if no bleeding, evaluate estrogen status with FSH
• FSH high: Ovarian failure
• FSH low or normal: Give cyclic estrogen and progesterone and, if menses start, diagnose chronic anovulation
• Estrogen absent (functional hypothalamic amenorrhea) or if menses doesn't start, diagnose Mullerian agenesis
• Prolactin high: Suspect prolactinoma, proceed with imaging the sella turcica
Lab
• If pregnancy test is negative
- Serum prolactin
- FSH
- TSH
- Blood sugar
ALERT
• Women 30 with ovarian failure should have karyotype analysis.
• Conditions that may alter lab results
- Pregnancy
- Menopause
- Hyperprolactinemia
- Ovarian suppression
- Endocrinopathy
Imaging
• Ultrasound may show cysts undetectable during pelvic examination, presence or absence of uterus, and endometrial thickness.
• Radiologic evaluation of the sella turcica, if prolactinoma suspected (elevated serum prolactin) or functional hypothalamic amenorrhea suspected, because adenomas can occur even with normal prolactin levels
Diagnostic Procedures/Surgery
• Laparoscopy: Diagnosis of the streak ovaries of Turner syndrome or PCOS (not often done)
• Hysterosalpingogram: To rule out Asherman syndrome, if it is the appropriate clinical situation
Pathological Findings
Due to underlying disease
DIFFERENTIAL DIAGNOSIS
• Includes all causes listed in "Etiology"
• The most common cause of secondary amenorrhea is pregnancy.
TREATMENT
STABILIZATION
Outpatient
GENERAL MEASURES
• Definitive treatment depends on determining the cause of the amenorrhea.
• May not be necessary to treat all cases, especially if just temporary amenorrhea.
Diet
Correct overweight or underweight by dietary management
Activity
No restrictions
MEDICATION (DRUGS)
First Line
• Progesterone replacement: Medroxyprogesterone (Provera) 5 mg b.i.d. for 5 days, will result in a withdrawal bleed if the hypothalamopituitary ovarian axis is intact and some endogenous estrogen production is present.
• Estrogen replacement: Conjugated estrogen, conjugated (Premarin) 0.625 mg for 25 days with progesterone added as above for the last 10 days will result in a withdrawal bleed, if the uterus and lower genital tract are normal.
• Use of hormonal therapies will not correct underlying problem. Other drugs might be required to treat specific conditions (e.g., bromocriptine for hyperprolactinemia).
• Use of hormonal replacement therapy is NOT recommended for long-term management of amenorrhea (1)[A]. It may be safe for short-term symptom management in young women (1)[C].
• Oral contraceptive pills or patches replace estrogen and prevent pregnancy and are probably the first-line drugs to use unless contraindicated. They also have a positive effect on bone mineral density in oligo/amenorrheic women (2)[B].
• Calcium supplementation 1,500 mg/d if cause is hypoestrogenism
• Because polycystic ovarian syndrome is related to insulin resistance, metformin (Glucophage) has been used (often starting at 500 mg b.i.d.) in an effort to correct metabolic abnormalities, improve ovulation (3)[A], and restore normal menstrual patterns (3)[B].
• Contraindications
- Pregnancy
- Thromboembolic disease
- Previous myocardial infarct, cerebrovascular accident
- Estrogen-dependent malignancy
- Severe hepatic impairment or disease
• Precautions
- Patients who are amenorrheic and wish to become pregnant should not be given hormone replacement therapy, but should receive treatment for infertility based on the specific cause.
- Diabetes with insulin resistance
- Seizure disorder
- Migraine headache
- Smoker >35
• Significant possible interactions
- Barbiturates
- Phenytoin
- Rifampin
- Corticosteroids
- Theophyllines
- Tricyclics
- Oral anticoagulants (anticoagulant effect may be decreased)
SURGERY
• Hymenectomy, done as a day surgery, required for those whose primary amenorrhea is due to imperforate hymen
• Lysis adhesions in Asherman syndrome
FOLLOW-UP
PROGNOSIS
• Reflects the underlying cause
• In secondary amenorrhea from hypothalamopituitary suppression, spontaneous resumption of menses with time (99% within 6 months) and correction of BMI
COMPLICATIONS
• Estrogen deficiency symptoms (e.g., hot flashes, vaginal dryness)
• Osteoporosis, in prolonged hypoestrogenic amenorrhea
• Increased risk of endometrial cancer in hyperestrogenism without progestin
PATIENT MONITORING
• Depends on the cause and treatment chosen
• If hormonal replacement is used, discontinuation after 6 months is advised to assess spontaneous resumption of menses.
REFERENCES
1. Farquhar CM, Marjoribanks J, et al. Long term hormonal therapy for perimenopausal and postmenopausal women. The Cochrane Database of Systematic Reviews, 2006.
2. Liu S, Lebrun C. Effect of oral contraceptive and hormone replacement therapy on bone mineral density in premenopausal and perimenopausal women: a systematic review. British Journal of Sports Medicine, 2006;40:11-24.
3. Andy C, Flake D. Do insulin-sensitizing drugs increase ovulation rates for women with PCOS? The Journal of Family Practice, 2005;54(2):156, 159-160.
MISCELLANEOUS
See also: Diabetes mellitus, Type 1; Diabetes mellitus, Type 2; Hyperthyroidism; Hypothyroidism, adult; Osteoporosis; Polycystic ovary syndrome

AMEBIASIS

2008-12-31T01:03:00.000-08:00

AMEBIASIS - Rodney D.Adam, MD
BASICS
DESCRIPTION
• Amebiasis is caused by the intestinal protozoan, Entamoeba histolytica. Infection results from ingestion of fecally contaminated food, such as garden vegetables, or by direct fecal-oral transmission. Most persons are asymptomatic or have minimal diarrheal symptoms; infection may be more severe in patients taking corticosteroids and other immunocompromised patients.
• In a few patients, invasive intestinal or extraintestinal (e.g., liver, and less commonly kidney, bladder, male or female genitalia, skin, lung, brain) infection results. Amebic abscess of the liver may develop during the acute attack or 1-3 months later; symptoms may be abrupt or insidious.
• E. histolytica has been divided into "pathogenic" and "nonpathogenic" strains. The pathogenic strains commonly cause invasive infection, while the noninvasive strains cause only asymptomatic intestinal infection. More recently, the nonpathogenic strains have been assigned to a separate species, Entamoeba dispar. Unfortunately, the species cannot be distinguished in a routine clinical laboratory.
• System(s) Affected: Gastrointestinal; Nervous; Renal/Urologic; Reproductive; Skin/Exocrine
• Synonym(s): Amebic colitis; Amebic dysentery
ALERT
Geriatric Considerations
More severe in elderly
Pediatric Considerations
More severe in neonates
Pregnancy Considerations
• More severe in pregnancy
• Most agents are avoided in pregnancy (especially first trimester) because of concerns of teratogenicity, but invasive disease must still be treated
- Paromomycin is sometimes recommended for noninvasive disease because it is not absorbed.
• Infectious disease consultation should be obtained.
GENERAL PREVENTION
Avoid risk factors when possible.
EPIDEMIOLOGY
• Predominant age: All
• Predominant sex: Male > Female; probably because of greater occupational exposure
Prevalence
Probably 1% overall, but much higher in some risk groups, such as areas with large immigrant populations
RISK FACTORS
• Low socioeconomic status
• Institutional living
• Male homosexuality
• Invasive disease is more common in certain geographic locations, including some parts of Mexico, South Africa, and India.
ETIOLOGY
Infection with E. histolytica is transmitted through contaminated food or water or person-to-person contact.

DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Noninvasive infection (up to 99%) (characteristic of E. dispar)
- Asymptomatic (90%)
- Mild diarrhea
- Abdominal discomfort
• Invasive intestinal infection
- Abdominal pain and tenderness
- Rectal pain
- Diarrhea
- Bloody stools
- Fever (30%)
- Systemic toxicity
• Extraintestinal infection
- Fever
- Systemic toxicity
- Right upper quadrant abdominal pain and tenderness
- Nausea and vomiting
- Diarrhea (50%)
- Hematuria, dysuria, urinary frequency and urgency
TESTS
Lab (1)[B], (2)[A]
• Stool for ova and parasites (unfortunately, the sensitivity of this exam is poor)
- Diarrheal stool should be examined immediately for trophozoites in addition to fixed stool specimens (repeated as necessary).
- In invasive intestinal infection, stools are bloody, but fecal leukocytes are usually absent.
• Serologic tests (especially indirect hemagglutination), positive in 85% of patients with colitis and most patients with extraintestinal disease
- Serologic tests should be done in patients with idiopathic inflammatory bowel disease to rule out amebiasis.
• In bladder infections: Amoebae and/or cysts in urine
• Liver enzymes and alkaline phosphatase may be elevated in hepatic disease.
• Drugs that may alter lab results
- Many drugs interfere with stool exams.
Imaging
CT scan or ultrasound for hepatic infection
Diagnostic Procedures/Surgery
• Rectosigmoidoscopy with biopsy
• Needle aspirate of hepatic lesions may be needed to rule out pyogenic infection or superinfection.
Pathological Findings
• Colon biopsy
- Lysis of mucosal cells (flask ulcers)
- Periodic acid-Schiff-stained trophozoites
- Neutrophils at the periphery
• Liver biopsy
- Necrosis surrounded by a rim of trophozoites
• Liver aspirate
- Red-brown material (anchovy paste)
DIFFERENTIAL DIAGNOSIS
• Other infectious causes of colitis
- Shigellosis
- Campylobacter infection
- Pseudomembranous colitis
- Occasionally salmonellosis or Yersinia infection
• Noninfectious causes of colitis
- Ulcerative colitis
- Crohn colitis
- Ischemic colitis
• Hepatic amebiasis must be distinguished from pyogenic liver abscess or superinfection of amebic abscess.
TREATMENT
STABILIZATION
Outpatient treatment
GENERAL MEASURES
• Fluids and nutrition
• Electrolyte management
Diet
As tolerated
Activity
In accordance with illness of patient
MEDICATION (DRUGS) (1)[B]
First Line
• Noninvasive infection
- Diiodohydroxyquin (also called iodoquinol): 650 mg t.i.d. PO for 20 days
• Invasive infection
- Metronidazole (Flagyl): 750 mg t.i.d. PO for 5-10 days, followed by a 20-day course of diiodohydroxyquin to eliminate intestinal carriage
- Tinidazole (Tindamax) 2 g daily for 3 days with food for intestinal infection and 2 g daily for 3-5 days for liver abscess
• Contraindications
- Diiodohydroxyquin: Use cautiously in patients with thyroid diseases. Contraindicated in hepatic or renal dysfunction. May cause optic neuritis or peripheral neuropathy.
- Known allergy to given medication
• Precautions
- None of the agents have been proven safe during pregnancy, but pregnant women with invasive disease should still be treated.
• Significant possible interactions
- Metronidazole and ethanol: Disulfiram reaction
Second Line
• Noninvasive infection
- Diloxanide 500 mg PO t.i.d. for 10 days
- Paromomycin 500 mg PO t.i.d. for 10 days
• Invasive infection
- Dehydroemetine (as effective as metronidazole, but cardiotoxic): 1-1.5 mg/kg/d IM for 5 days
- Chloroquine (less effective): 600 mg base/d PO for 2 days, then 200 mg/d PO for 2-3 weeks (pediatric dose: 10 mg/kg/d up to maximum of 300 mg/d)
SURGERY
With severe amebic colitis, surgery may be necessary for necrosis or perforation.
FOLLOW-UP
PROGNOSIS
• Untreated invasive amebiasis is frequently fatal.
• With treatment, improvement usually occurs within a few days.
• Some patients with amebic colitis have irritable bowel symptoms for weeks after successful treatment.
• Relapses possible
COMPLICATIONS
• Toxic megacolon with rupture
• Rupture of hepatic abscess, which may perforate into subphrenic space, right pleural cavity, or other nearby organs
• Bladder perforation, urethral strictures, vesicointestinal fistula
PATIENT MONITORING
• Patient signs and symptoms
• Stool for ova and parasite
REFERENCES
1. Haque R,Huston CD,Hughs M,Houpt E,Petri WA Jr. Amebiasis. N Engl Journ Med. 2003;348: 1565-1573.
2. Tanyuksel M,Petri WA Jr. Laboratory diagnosis of amebiasis. Clin Microbiol Rev.2003;16:713-729.

AMBLYOPIA

2008-12-31T01:00:00.000-08:00

AMBLYOPIA - Robert M.Kershner, MD
BASICS
DESCRIPTION
Amblyopia is the reduction in visual acuity in an eye due to not receiving adequate usage in early childhood; there is no structural or pathological abnormality of the eye, and it cannot be corrected by eye glasses or contact lens. Strabismus is the inability to align both eyes simultaneously under normal conditions.
• When seen in the geriatric population, the diagnosis has usually been made early in childhood.
• System(s) Affected: Nervous
• Synonym(s): Lazy eye
ALERT
Pediatric Considerations
More commonly seen in the pediatric age group early in life
GENERAL PREVENTION
None
EPIDEMIOLOGY
• Predominant age: May be present from birth or may be detected at any age
• Predominant sex: Male = Female
Prevalence
~2-2.5% in the general population
RISK FACTORS
None identified
Genetics
Increased incidence in children with one parent with a history of amblyopia
PATHOPHYSIOLOGY
• Strabismic amblyopia is a loss of visual acuity in an individual due to suppression of the images in an eye, which turns out or in.
• Anisometropic amblyopia is present when 1 eye has a significantly different refractive error than the fellow eye, leading to visual blurring.
• Refractive amblyopia is due to uncorrected high refractive error, resulting in visual blurring in either or both eyes.
• Deprivation amblyopia (amblyopia ex anopsia) is due to relatively complete visual deprivation in one eye, which may be caused by a congenital abnormality such as a corneal scar or cataract.
• Deficiency amblyopia is also known as nutritional optic neuropathy or tobacco-alcohol amblyopia. Deficiencies of vitamins B1 or B12, or riboflavin, may be responsible.
ETIOLOGY
• See "Pathophysiology."
ASSOCIATED CONDITIONS
• Amblyopia is more common in families with a history of unequal refractive errors, high uncorrected refractive errors, and strabismus.

DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Rubbing the eyes
• Sitting close to television or computer screen
• Problems in sports
• Preference for front-row seating
• Covering or closing an eye
• Squinting eye in bright light
• Eye turns "in" or "out"; wandering eye
• Poor vision in one eye without apparent explanation
• Poor vision that does not correct with glasses
Physical Exam
• Examination by an ophthalmologist to screen for unequal refractive error, outward or inward turning of the eye (strabismic amblyopia), and proper vision testing of the eye under monocular conditions.
• All children should have complete visual examinations prior to starting school, with each eye tested individually. Children from families with a known history of amblyopia or strabismus should have special exams by an ophthalmologist.
TESTS
Diagnostic Procedures/Surgery
A complete slit lamp and dilated funduscopic examination is necessary to exclude an organic cause for the decreased visual acuity.
DIFFERENTIAL DIAGNOSIS
The diagnosis of amblyopia can be confused with an organic lesion causing decreased visual acuity, and this must always be excluded before the diagnosis of amblyopia is considered.
TREATMENT
STABILIZATION
Outpatient treatment
GENERAL MEASURES
• Correction of the underlying disorder should be instituted at the earliest opportunity.
• Full refractive correction and/or patching of the stronger eye to encourage visual development of the amblyopic eye is warranted.
• Amblyopia never corrects itself spontaneously and will always require treatment. Children do not outgrow amblyopia.
• Deficiency amblyopia: Balanced diet, vitamins, and avoidance of alcohol and tobacco
Diet
No special diet
Activity
No restrictions
SURGERY
Surgical correction of an abnormal eye position may be required.
FOLLOW-UP
PROGNOSIS
A treatable condition in most cases if the diagnosis is made early
• Patching therapy, eyeglasses, and surgical correction of abnormal eye positions can result in near normalcy of vision when instituted early.
• Visual development occurs during 1st several years of life, and amblyopia therapy can be effective until ~age 12.
COMPLICATIONS
If there is failure to institute proper therapy early, permanent and profound visual loss can be expected.
PATIENT MONITORING
Once the diagnosis of amblyopia is made, the patient needs to be seen frequently at the discretion of the ophthalmologist until complete resolution of the problem occurs.
REFERENCES
1. American Academy of Ophthalmology. Binocular Vision and Ocular Motility, 1985-1986 (Ophthalmology Basic and Clinical Science Course, Section 6). San Francisco: American Academy of Ophthalmology, 1985.
2. Harley RD. Pediatric Ophthalmology. Philadelphia PA: Saunders,1983.

ALZHEIMER DISEASE

2008-12-30T22:53:00.000-08:00

ALZHEIMER DISEASE - Jill A.Grimes, MD
BASICS
DESCRIPTION
• Most common cause of dementia in the elderly.
• Degenerative neurologic disease characterized by progressive cognitive and behavioral impairment, usually occurring >65 years of age.
• Diagnosis of exclusion; cost in US >$110 billion/year.
• Usual course: Progressive and chronic
• System(s) Affected: Nervous
• Synonym(s): Presenile dementia; Senile dementia of the Alzheimer type
ALERT
Geriatric Considerations
The US Preventive Services Task Force states evidence is lacking to recommend for or against routine screening for dementia in elderly patients without complaints of memory loss (5).
GENERAL PREVENTION
• Studies of NSAIDs, prednisone, estrogen, and vitamin E have not been shown to delay Alzheimer disease (1,2)[A].
• HRT is not recommended (6)[A].
• Intellectual challenge (puzzles) and regular physical exercise may offer preventive benefit.
EPIDEMIOLOGY
• Predominant age: >60
• Predominant sex: Female > Male (slightly)
Incidence
40% of those >85 are affected, which is 1,100/100,000 people.
RISK FACTORS
• Aging
• Low education level
• Down syndrome
• Positive family history
• Inheritance of the E4 allele of apolipoprotein E gene on chromosome 19 (E4 is a much less of a risk factor for African Americans and Hispanics)
• Smoking (2-4-fold increase)
Genetics
Positive family history in 50% of the cases, but 90% of AD cases are sporadic.
ETIOLOGY
• Unknown, but toxic -amyloid deposits in neuritic plaques and arterial walls appear critical to pathogenesis.
• -Amyloid precursor gene localized to chromosome 21
ASSOCIATED CONDITIONS
• Down syndrome
• Depression

DIAGNOSIS
SIGNS AND SYMPTOMS
• No focal neurologic signs
• Short term memory loss
• Acalculia (e.g., cannot balance check book)
• Agnosia: Inability to recognize objects
• Apraxia: Inability to carry out movements
• Confabulation
• Delusions
• Impaired abstraction
• Decreased attention to hygiene
• Visuospatial distortion
• Late signs
- Psychotic features
- Mutism
History
Include family members in interview (helpful in assessment of behavioral changes, patients).
• Progressive memory loss
• Depression
• Apathy
• Anhedonia
• Intellectual decline
• Loss of interest; social withdrawal
• Occupational dysfunction
• Personality change
• Progressive cognitive impairment
• Restlessness
• Sleep disturbances
• Weight loss
• Incontinence
Physical Exam
• Complete neurologic exam to rule out other causes of dementia
• Folstein mini mental status exam
TESTS
• Lumbar puncture
• Neuropsychologic testing (if clinical picture is confusing or to help determine level of independence for skills such as balancing checkbooks, driving, or managing medicines)
Lab
• To help rule out other causes of dementia (3)[C].
• CBC
• Chemistry panel
• TSH
• Folate and B12 levels
• VDRL or RPR
• Sedimentation rate
• HIV antibody (selected cases)
• Family may have genetic testing for E4 allele of apolipoprotein E gene; not recommended.
Imaging
• Controversy exists concerning cerebral imaging (2,3)[C].
• An MRI or CT is needed to rule out other diagnoses, if cognitive decline is recent, there is history of stroke, or focal neurologic signs are present.
• CT/MRI: Moderate cortical atrophy, ventricular enlargement
• MRI: Hippocampal volumetry; positron emission tomography (PET) and single photon emission computed tomography (SPECT) not indicated.
• Medicare pays for PET to distinguish Alzheimer from frontotemporal dementia.
Pathological Findings
• Gross
- Diffuse cerebral atrophy in hippocampus, amygdala, and some subcortical nuclei
• Micro
• Neuritic senile plaques
- Neurofibrillary tangles
- Pyramidal cell loss
- Decreased cholinergic innervation (other neurotransmitters variably decreased)
- Degeneration of locus ceruleus and basal forebrain nuclei of Meynert; amyloid angiopathy
DIFFERENTIAL DIAGNOSIS
• Vascular dementia; multi-infarct dementia
• Lewy body disease
• Dementia associated with Parkinson disease
• Normal pressure hydrocephalus
• Creutzfeldt-Jakob disease
• End-stage multiple sclerosis
• Brain-tumor: Primary or metastatic
• Subdural hematoma
• Progressive multifocal leukoencephalopathy
• Metabolic dementia (hypothyroidism)
• Drug reactions
• Alcoholism and other addictions
• Dementia pugilistica
• Depression
• Toxicity from liver and kidney failure
• Vitamin and other nutritional deficiencies
• Vasculitis
• Neurosyphilis
TREATMENT
GENERAL MEASURES
• Appropriate supportive care
• Outpatient, day care, assisted living, skilled nursing facility
• Optimize treatment of associated comorbidities
• Occupational therapy
• Music therapy
• Analyze environment for safety and security
• Assess needs of spouse/caregiver
• Advance directives planning
Diet
Nutritional supplements in later stages
Activity
• Exercise to reduce restlessness
• Continued cognitive challenge
Complementary and Alternative Medicine
• Randomized trials of Ginkgo biloba have produced conflicting results (1)[A].
• Coenzyme Q10, Huperzine not effective
MEDICATION (DRUGS)
• Memory enhancement
- Anticholinesterase inhibitors (1,2)[A]: Donepezil (Aricept) 5-10 mg/d, rivastigmine (Exelon) 3-6 mg b.i.d., or galantamine (Razadyne) 8-12 mg b.i.d.
- Best in mild to moderate disease (Folstein MMSE scores 10-24); may show small benefit in more severe disease. Drugs may be effective in Lewy body dementia.
- Only 30-40% of the patients will respond, either by modest improvement or slowed decline over 1-2 years. Unlike tacrine, no liver toxicity seen. Most common side effects are gastrointestinal.
First Line
• No specific drug therapy available for halting disease. Clinical studies are ongoing
• Use as few drugs as possible
• No drugs are helpful for wandering, restlessness, uncooperativeness, hoarding, and irritability. Use behavioral techniques and environmental modification (2)[C].
• For depression (occurs in 1/3 of patients), use selective serotonin reuptake inhibitors (SSRIs).
• Insomnia
- Trazodone 25-100 mg at bedtime, zolpidem (Ambien) 5 mg at bedtime, zaleplon (Sonata) 5-10 mg at bedtime, ramelteon (Rozerem) 8 mg at bedtime.
- Avoid diphenhydramine in elderly males, which can cause urinary retention.
• Moderate anxiety/restlessness
- Consider low-dose, short-acting benzodiazepines, buspirone, or SSRIs, but efficacy unproven
• Severe aggressive agitation (especially if psychotic features present)
- Risperidone (Risperdal) 0.25-1.0 mg b.i.d., olanzapine 2.5 mg/d b.i.d.; other newer atypical antipsychotic agents now preferred due to fewer side effects (2)[C].
- Attempt periodic dose reductions or discontinuation, especially in a nursing home patient (see Omnibus Reconciliation Act [OBRA] 1987)
- Anticholinesterase inhibitors also help behavioral symptoms (4,5)[A].
- Carbamazepine (Tegretol) 100 mg b.i.d.-t.i.d., propranolol (Inderal) 10-40 mg b.i.d.-t.i.d., trazodone 200 mg/d, and valproic acid 250-1,500 mg/d (2)[C].
- SSRIs are also being tried
- Memantine (Namenda) (1)[A], 1st of new class of N-methyl-d-aspartate receptor antagonists; can be used as monotherapy or in combination with acetylcholinesterase inhibitors to enhance or preserve memory. Start 5 mg/d, titrating to target dose of 10 mg b.i.d. after 4 weeks. Shows efficacy in severe disease (MMSE 5-14).
• Contraindications
- Avoid anticholinergic drugs, such as tricyclic antidepressants and antihistamines.
- Ginkgo biloba: Avoid anticoagulants and aspirin
• Precautions
- Benzodiazepines may produce paradoxical excitation or daytime drowsiness
- Triazolam (Halcion) can produce confusion, memory loss, and psychotic behavior.
- Atypical antipsychotic agents have been associated with hyperglycemia, ketoacidosis, increased stroke risk, and increased mortality in elders and dementia cases.
- Anticholinesterase inhibitors provide only modest benefit for 1-2 years, after which decline continues at somewhat lesser rate than placebo. NNT is 7. No deterioration over 6-12 months is evidence of efficacy (1,2)[A].
- Significant possible interactions
- Antipsychotics: Lithium may induce extrapyramidal symptoms and disorientation.
- Benzodiazepines may increase serum phenytoin concentration; cimetidine may increase the benzodiazepine concentration.
- Donepezil (Aricept): Use with caution with anticholinergic medication or in patients with sick sinus syndrome or a history of peptic ulcers. Avoid paroxetine (Paxil), which causes increases donepezil levels.
Second Line
Studies reveal conflicting efficacy of selegiline 5 mg b.i.d., vitamin E, 1,000 b.i.d. or NSAIDS in slowing the progression of the disease (1,2)[A].
FOLLOW-UP
DISPOSITION
Issues for Referral
• Visiting nurse
• Social worker
• Physical therapist
• Occupational therapist
• Lawyer (living will, power of attorney)
• Support groups for patient and family
• Assess driving safety
PROGNOSIS
Poor: Average survival is 4-6 years
COMPLICATIONS
• Behavioral
- Hostility, agitation, wandering, uncooperativeness
• Metabolic
- Infection, dehydration, drug toxicity, malnutrition
• Other
- Falls "Sundowning"
- Depression (1/3 of patients)
- Suicide: In early stages, if depressed
PATIENT MONITORING
• As often as necessary to treat poor nutrition, medical complications, provide support for family, assess need for placement
• Serial mental status testing potentially helpful, but bedside tests (MMSE) offer wide variability and lack of sensitivity
• Monitor caregiver burnout
REFERENCES
1. AHRQ report # 97. Pharmacological treatment of dementia. US Department of Health and Human Services, 2004.
2. Clark CM, Karlawish JH. Alzheimer disease: Current concepts and emerging diagnostic and therapeutic strategies. Ann Intern Med. 2003;138:400-410.
3. Knopman DS, Boeve BF, Petersen RC. Essentials of the proper diagnosis of MCI, dementia and major subtypes of dementia. Mayo Clinic Proc. 2003;78(10):290-308.
4. Sink KM, Holden KF, Yeffe K. Pharmacological treatment of neuropsychological symptoms of dementia. JAMA. 2005;293:596-608.
5. Trinh NH, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: A meta-analysis. JAMA. 2003;289:210-216.
6. Hogervorst E, Yaffe K, Richards M, Huppert F. Hormone replacement therapy for cognitive function in postmenopausal women. Cochrane Database of Systematic Rev. 4, 2006.
MISCELLANEOUS
See also: Alcohol use disorders; Hypothyroidism; Depression

ALTITUDE ILLNESS

2008-12-30T22:50:00.000-08:00

ALTITUDE ILLNESS - Robert Hyde, MD, MA, EMT-P
BASICS
DESCRIPTION
A spectrum of medical problems ranging from mild discomfort to fatal illness that may occur on ascent to higher altitude (elevations above 1,500 meters [4,921 feet]); is divided into 3 categories: High 1,500-3,500 m, very high 3,500-5,500 m, and extreme 5,500-8,850 m. (1) It can affect anyone, including the most experienced and fit individual. For most, is an unpleasant but self-limiting syndrome that will not require physician intervention.
• Acute mountain sickness (AMS): Symptoms associated with a physiologic response to a hypobaric, hypoxic environment. Onset occurs within 24 hours of arrival at altitude; often within 1-4 hours. Neurologic symptoms are predominant, and range from mild to moderate headache and malaise to severe impairment.
• High-altitude pulmonary edema (HAPE): Noncardiogenic pulmonary edema. Onset within 1-4 days at altitude. Rare below 8,000 feet (2,438 m).
• High-altitude cerebral edema (HACE): A potentially fatal neurologic syndrome; considered the end stage of AMS. Onset within 3-5 days at elevation as low as 2,750 m (9,022 feet), but may be more abrupt at higher altitudes. Death results from brain herniation.
• System(s) Affected: Nervous; Pulmonary
• Synonym(s): Mountain sickness
ALERT
Geriatric Considerations
• Risk does not increase with age.
• Age alone should not preclude travel to high altitude; allow extra time to acclimate.
• Pre-existing medical problems made worse are referred to as altitude-exacerbated conditions.
Pediatric Considerations
• Altitude illness seems to have the same incidence in children as in adults, but diagnosis may be delayed in younger children.
• Any child who experiences behavioral symptoms after recent ascent should be presumed to be suffering from altitude illness.
Pregnancy Considerations
• The risk during pregnancy is unknown.
• No evidence that exposure to high altitude (1,500-3,500 m) poses a risk to a pregnancy
• It may be prudent to advise a low-altitude dwelling to any pregnant woman experiencing complications.
GENERAL PREVENTION
• General guidelines
- Preacclimatization affords some protection against altitude illness.
- Staged or graded ascent (rest day every 600-1,200 m) and a slow ascent rate (maximum 600 m/day) should allow adequate time for acclimatization.
- Sleeping elevation: "Climb high and sleep low" is a prudent practice for anyone going above 3,500 m
- Avoid heavy exertion for the 1st 1-3 days.
- Avoid respiratory depressants such as alcohol and soporifics.
- Pre-ascent physical conditioning is not preventive.
• Drug prophylaxis
- Acetazolamide (if patient has a history of problems at altitude and/or plans to ascend >500 m/d). Dosage is usually 125-500 mg PO b.i.d. starting 2 days before ascent and continued for 3 days at maximum altitude. Patients with a drug allergy to sulfonamides should avoid acetazolamide.
- Dexamethasone may significantly reduce the incidence and severity of acute mountain sickness. Dosage is 2-4 mg PO q6h, begun the day of ascent, continued for 3 days at the higher altitude, then tapered over 5 days. Adverse side effects are rare.
- For HAPE only
 Consider nifedipine 30 mg extended-release PO b.i.d. start prior to ascent and continue for 2 days at maximum altitude.
 Consider beta-agonists (salmeterol, albuterol) 125 mcg inhaled b.i.d. starting 1 day before ascent and 2 days at maximum altitude.
EPIDEMIOLOGY
Most epidemiologic studies are limited to relatively homogenous populations of men.
Incidence
• AMS: 10-90% globally
• HAPE/HACE: 0.01-1% of sojourner ascents at typical mountain resorts, although incidence increases with rapid and higher ascents (2)
Prevalence
Unknown
RISK FACTORS
• Rapid rate of ascent
• Maximum altitude attained
• Increased duration at high altitude
• Failure to acclimatize at lower altitude
• Increased sleeping altitude
• Prior history of altitude illness
• Cardiac congenital abnormalities
PATHOPHYSIOLOGY
• Not completely understood
• Hypobaric hypoxia and hypoxemia are the pathogenetic precursors to altitude illness.
• Symptoms of AMS may be the result of cerebral swelling, either through vasodilatation induced by hypoxia or through cerebral edema.
• Other mechanisms include impaired cerebral autoregulation, release of vasogenic mediators, and alteration of the blood-brain barrier
• HAPE is a noncardiogenic pulmonary edema characterized by exaggerated pulmonary hypertension leading to vascular leakage through overperfusion, stress failure, or both.
ETIOLOGY
Individuals with a prior episode of HAPE have an increased risk of recurrence. (3)

DIAGNOSIS
SIGNS AND SYMPTOMS
• AMS, mild to moderate symptoms
- Headache, plus at least 1 of the following
 Anorexia
 Nausea or vomiting
 Dizziness or lightheadedness
 Insomnia
• AMS, severe symptoms
- Increased headache
- Irritability
- Marked fatigue
- Dyspnea with exertion
- Nausea and vomiting
• HAPE (Lake Louise diagnostic criteria)
- At least 2 of the following symptoms
 Dyspnea at rest
 Cough
 Weakness
 Decreased exercise performance
 Chest tightness
 Congestion
- AND at least 2 of the following signs
 Crackles or wheezing in at least 1 lung field
 Central cyanosis
 Tachycardia
 Tachypnea
- Note: Fatigue may be pulmonary edema
• HACE symptoms
- Mental status changes (irrational behavior, lethargy, obtundation, coma)
- Truncal ataxia
- Papilledema, retinal hemorrhage, cranial nerve palsies
- Focal neurologic deficits (rare)
TESTS
ECG may show sinus tachycardia, or right-sided heart strain.
Lab
• AMS: Laboratory studies are nonspecific and rarely required for diagnosis.
• HAPE: Severe hypoxemia demonstrated with oximetry or blood gas analysis.
Imaging
No radiographic feature is specific to HAPE.
DIFFERENTIAL DIAGNOSIS
Onset of symptoms >3 days at a given altitude, the absence of headache or the lack of rapid response to oxygen or descent suggest other diagnoses
• AMS/HACE
- Subarachnoid hemorrhage; central nervous system (CNS) mass; cerebrovascular accident (CVA)
- Migraine headache
- Dehydration
- Ingestion of toxins, drugs, or alcohol
- Carbon monoxide exposure
- CNS infection
- Acute psychosis
• HAPE
- Pneumonia
- Cardiogenic pulmonary edema
- Spontaneous pneumothorax
- Pulmonary embolism
- Asthma, bronchitis
- Myocardial infarction
- Hyperventilation syndrome
TREATMENT
STABILIZATION
Outpatient treatment for mild cases
GENERAL MEASURES
• Therapy must be tailored to fit disease severity
• Early recognition is critical.
• Stop ascent, acclimatize at the same altitude and/or descend if symptoms do not improve over 24 hours. Definitive treatment is to descend to a lower altitude. Dramatic improvement accompanies even modest reductions in altitude.
• Oxygen helps relieve symptoms. Give continuously by cannula or mask initially, then titrate to SaO2 >90%
• AMS
- Acetazolamide is effective in reducing mild to moderate symptoms of AMS, but the optimum dosage is unknown. Consider 125-500 mg PO b.i.d. until symptoms resolve.
- Dexamethasone may also be effective in treating moderate AMS. Consider 4 mg PO/IM/IV q6h.
- Analgesics and antiemetics as needed for symptomatic relief
• HAPE
- Oxygen therapy
- Minimize exertion and keep patient warm
- Immediate descent or evacuation to a lower altitude
- Portable hyperbaric therapy (2-15 psi), such as the Gamow bag or Chamberlite, is an effective and practical alternative when descent is not possible.
- Consider nifedipine 10 mg PO, then 20-30 mg extended release PO b.i.d.
• HACE
- Immediate descent
- Supplemental oxygen (highest flow available; maintain SaO2 >90%)
- Dexamethsone 8 mg IV/IM/PO initially, then 4 mg q6h
- Hyperbaric therapy if unable to descend
Activity
Rest until symptoms clear
MEDICATION (DRUGS)
First Line (4-6)[B]
• Oxygen: 2-15 L/min to maintain SaO2 >90% until symptoms improve
• Acetozolamide:
- Prevention of AMS: 125-500 mg PO b.i.d. starting 1 day before ascent and continued for 2 days at maximum altitude
- Treatment of AMS: 125-500 mg PO b.i.d. until symptoms resolve
• Dexamethasone:
- Prevention of AMS: 2 mg PO q6h or 4 mg PO q12h, starting 1 day before ascent and discontinued cautiously after 2 days at maximum altitude
- Treatment of AMS: 4 mg PO/IV/IM q6h
- Treatment of HACE: 8 mg PO/IV/IM initially, then 4 mg q6h
• Nifedipine (reduces pulmonary artery pressure):
- Prevention of HAPE: 20-30 mg extended-release PO b.i.d. starting 1 day prior to ascent and continued for 2 days at maximum altitude
- Treatment of HAPE: 10 mg, then 20-30 mg extended-release PO b.i.d.
• Salmeterol:
- Prevention and possible treatment of HAPE: 125 mcg inhaled b.i.d. starting 1 day before ascent and continued for 2 days at maximum altitude
• NSAIDs:
- Prevention and treatment of headache
- Aspirin 325 mg PO q4h for total 3 doses
- Ibuprofren 400-600 mg PO
- Prevention of AMS: Dose unknown. Begin 1-5 days before ascent.
• Antiemetics:
- Prochlorperazine 10 mg PO/IM q6-8h
- Promethazine 25-50 mg PO/IM/PR q6h
• Contraindications: Refer to manufacturer's profile for each drug.
• Precautions: Refer to manufacturer's profile for each drug.
• Significant possible interactions: Refer to manufacturer's profile of each drug.
Second Line
Furosemide:  Consider for treatment of AMS or HACE, 20-80 mg PO/IV q12h for total 2 doses. Currently out of favor; not recommended for prophylaxis; not established for use in HAPE
FOLLOW-UP
DISPOSITION
Admission Criteria
Severe cases
PROGNOSIS
Most cases of mild to moderate AMS are self-limiting and do not require physician intervention. Patients may resume ascent once symptoms subside. HAPE and HACE respond well to descent, evacuation, and/or pharmacologic treatment if identified early.
COMPLICATIONS
Patient may experience high-altitude retinal hemorrhage (HARH), which can cause visual changes, but is usually asymptomatic.
PATIENT MONITORING
• For mild cases, no follow-up needed.
• For more severe cases, follow until symptoms subside.
REFERENCES
1. Gallagher SA, Hackett PH. High-altitude Illness. Emerg Med Clin N Am. 2004;22:329-355.
2. Maloney JP, Broeckel U. Epidemiology, risk factors, and genetics of high-altitude-related pulmonary disease. Clin Chest Med. 2005;26:395-404.
3. Basnyat B, Murdoch DR. High-altitude Illness. The Lancet. 2003;361:1967-1973.
4. Hackett PH, Roach RC. High-Altitude Illness. NEJM. 2001;345(pt 2):107-114.
5. Barry PW, Pollard AJ. Altitude Illness. BMJ. 2003;326:915-919.
6. Dumont L, Mardirosoff C, Tramer MR. Efficacy and harm of pharmacological prevention of acute mountain sickness: quantitative systematic review. BMJ. 2000;321:267-272.
7. Rodway GW et al. High-altitude-related disorders, Part I: Pathophysiology, differential diagnosis and treatment. Heart and Lung. 2003;32(6):353-359.
8. Rodway GW, et al. High-altitude-related disorders, part II: Prevention, special populations and chronic medical conditions. Heart and Lung. 2003;33(1): 3-12.
ADDITIONAL READING
For further information about hyperbaric therapies, oxygen systems, and protocols, visit http://www.ismmed.org and www.high-altitude-medicine.com.

ALOPECIA

2008-12-30T22:47:00.000-08:00

ALOPECIA - Aubrey L.Knight, MD
BASICS
DESCRIPTION
• Absence of the hair from skin areas where it normally is present. Anagen hairs are growing hairs. Telogen hairs are dead "resting" hairs.
• Telogen effluvium: Diffuse hair loss that (usually) results in temporarily decreased hair density but does not progress to complete baldness.
• Anagen effluvium: Diffuse shedding of hairs, including growing hairs, that may progress to complete baldness.
• Cicatricial alopecia: Also known as scarring alopecia; characterized by slick, smooth scalp without any evidence of follicular openings of hair.
• Androgenic alopecia: Hair loss occurring in either sex, caused by stimulation of the hair roots by male hormones, more common after age 50.
• Alopecia areata: Patchy, nonscarring hair loss.
• Traction alopecia: Patchy, initially nonscarring hair loss due to pulling on the hair.
• Tinea capitis: Patches of hair broken off close to the scalp ("Black dot"), with/without associated inflammation, caused by fungus infection.
• Trichotillomania: Intentional pulling out of otherwise healthy hair; is usually due to habit.
ALERT
Pediatric Considerations
Tinea capitis is the only common form of alopecia.
Pregnancy Considerations
Postpartum hair loss is due to altered physiology during pregnancy.
EPIDEMIOLOGY
• Predominant age
- Incidence of androgenic alopecia increases with age.
- Tinea capitis and traction alopecia more common in children
• Predominant sex: Male > Female
Prevalence
• 50% of white men have noticeable male-pattern baldness by 50 years of age.
• 37% of postmenopausal females show some evidence of hair loss.
RISK FACTORS
• Positive family history of baldness
• Physical or psychologic stress
• Pregnancy
• Poor nutrition
Genetics
• In whites, androgenic alopecia follows a dominant trait with incomplete penetrance.
• Hereditary incidence notable in men and women with a strong family history of baldness
PATHOPHYSIOLOGY
See "Description"
ETIOLOGY
• Telogen effluvium
- Postpartum
- Drugs (oral contraceptives, anticoagulants, retinoids, -blockers, chemotherapeutic agents, interferon)
- Stress (physical illness, fever, or psychologic)
- Hormonal (hypo- or hyperthyroidism, hypopituitarism)
- Nutritional (malnutrition, iron deficiency, zinc deficiency)
- Diffuse alopecia areata
• Anagen effluvium
- Mycosis fungoides
- X-ray treatment
- Drugs (chemotherapeutic agents, allopurinol, levodopa, bromocriptine)
- Poisoning (bismuth, arsenic, gold, boric acid, thallium)
• Cicatricial alopecia
- Congenital and developmental defects
- Infection (leprosy, syphilis, varicella zoster, cutaneous leishmaniasis)
- Basal cell carcinoma
- Epidermal nevi
- Physical agents (acids and alkali, burns, freezing, radiodermatitis)
- Cicatricial pemphigoid
- Lichen planus
- Discoid lupus erythematosus
- Sarcoidosis
• Androgenic alopecia
- Adrenal hyperplasia
- Polycystic ovaries
- Ovarian hyperplasia
- Carcinoid
- Pituitary hyperplasia
- Drugs (testosterone, danazol, adrenocorticotropic hormone, anabolic steroids, progesterones)
• Alopecia areata
- Unknown, but possibly autoimmune
• Traction alopecia
- Trichotillomania (direct self-pulling of the hair)
- Tight rollers or braids
• Tinea capitis
- Microsporum sp.
- Trichophyton sp.
ASSOCIATED CONDITIONS
Alopecia areata
• Down syndrome
• Vitiligo
• Diabetes

DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Hair loss
• Pruritus (in tinea capitis)
Physical Exam
• Scaling of the scalp (in tinea capitis)
• Broken hairs (in tinea capitis and traction alopecia)
• Tapered hair at the borders of the patch of alopecia (in alopecia areata)
• Easily removable hairs at the periphery of the patch of alopecia (in alopecia areata)
• Inflammation (in tinea capitis)
• Hair-pull test: 3 cm above ear, pinch 20-40 hairs and exert slow, gentle traction while sliding fingersup hair shaft. Telogen(aka "club") hair bulbs are unpigmented and ovoid. Anagen hairs have elongated and possibly pigmented bulb with gelatinous root sheath.
• Light hair-pull test (positive if anagen hairs come loose easily; seen in alopecia areata)
• Hair pull test with >6 club hairs consistent with telogen effluvium
TESTS
Lab
Consider
• TSH
• CBC (may reflect an underlying immunologic disorder or anemia)
• Free testosterone and dehydroepiandrosterone sulfate in women with androgenic alopecia
• Serum ferritin
• VDRL or RPR for syphilis
• Lymphocyte T- and B-cell number (sometimes low in patients with alopecia areata)
• Drugs that may alter lab results:Thyroid drugs and iodine preparations (including topicals) will alter thyroid tests.
Diagnostic Procedures/Surgery
• Direct microscopic examination of the hair shaft
• Potassium hydroxide examination of the scale, if present (positive in tinea capitis)
• Fungal culture of the scale, if present
• Scalp biopsy (sometimes)
• Drugs that may alter lab results:Antifungal drugs may make potassium hydroxide examination falsely negative.
Pathological Findings
Scalp biopsy with routine microscopy and direct immunofluorescence will aid in the diagnosis of tinea capitis, diffuse alopecia areata, and the scarring alopecias due to lupus erythematosus, lichen planus, and sarcoidosis
DIFFERENTIAL DIAGNOSIS
Search for type of alopecia and then for possible reversible causes.
TREATMENT
STABILIZATION
Outpatient treatment
GENERAL MEASURES
• Traction alopecia
- Only with discontinuation of the hair pulling will the disorder resolve.
- Psychologic or psychiatric intervention may be necessary.
- Successful therapeutic approaches have included medications, behavior modification, and hypnosis.
• Tinea capitis
- 6-8 weeks of oral therapy are often necessary. Topical medications are ineffective.
- Careful hand washing and laundering of head wear and towels
Diet
No special diet
MEDICATION (DRUGS)
• Androgenic alopecia: Topical minoxidil (Rogaine) 2%; finasteride (Propecia), 1 mg PO daily
• Alopecia areata: High-potency topical steroids, topical anthralin, intralesional steroids, psoralen with long-wave UV radiation, cyclosporine
• Tinea capitis: Griseofulvin (ultramicrosize) 250-375 mg/d PO in adults, 5.5-7.3 mg/kg/d in children. Alternatively, ketoconazole 200 mg/d PO. Treatment for 6-8 weeks.
• Contraindications
- Griseofulvin: Pregnancy, porphyria, hepatocellular failure
- Ketoconazole and cisapride (Propulsid) should not be used together.
- Itraconazole and cisapride should not be used together.
• Precautions
- Topical minoxidil
 Burning and irritation of the eyes
 Salt and water retention
 Tachycardia
 Angina (rare)
- Topical steroids
 Local burning and stinging
 Pruritus
 Skin atrophy
 Telangiectasias
 Hypothalamic-pituitary-adrenal (HPA) suppression if high-potency steroids used for prolonged duration
- Griseofulvin
 Photosensitivity reaction
 Lupuslike syndrome
 Oral thrush
 Granulocytopenia
- Ketoconazole
 Anaphylaxis
 Hepatotoxicity
 Oligospermia
 Neuropsychiatric disturbances
 Gynecomastia
- Itraconazole
 Hepatotoxicity
 Nausea, vomiting
- Finasteride
 Not indicated for use in women
 Caution when there is liver disease
• Significant possible interactions
- Griseofulvin and warfarin: Decreased activity of warfarin
- Griseofulvin and barbiturates: Depressed activity of griseofulvin
- Ketoconazole and warfarin: May enhance activity of warfarin
- Ketoconazole and isoniazid, rifampin: Decreased activity of ketoconazole
- Ketoconazole and phenytoin: May alter metabolism of either drug
- Itraconazole and terfenadine: Prolonged QT and ventricular arrhythmias
- Itraconazole and astemizole: Prolonged QT and ventricular arrhythmias
- Itraconazole and cisapride: Contraindicated
- Itraconazole and digoxin: May result in elevated levels of digoxin
- H2 blockers or antacids and ketoconazole: Decreased absorption of ketoconazole. If necessary, give H2 blocker or antacids at least 2 hours after ketoconazole dose. Avoid using the proton pump inhibitor omeprazole for the same reason.
SURGERY
• Androgenic alopecia: Hair transplantation, scalp reduction, transposition flap, and soft-tissue expansion.
• Cicatricial alopecia: Only effective treatment is surgical (graft transplantation, flap transplantation, or excision of the scarred area).
FOLLOW-UP
PROGNOSIS
• Telogen effluvium
- Maximum shedding 3 months after the inciting event (medication, stress, nutritional deficiency) and recovery following correction of the cause
- Rarely permanent baldness
- Chronic effluvium uncommon
• Anagen effluvium
- Shedding begins days to a few weeks after the inciting event, with recovery following correction of the cause.
- Rarely permanent baldness
• Cicatricial alopecia
- Hair follicles permanently damaged
• Androgenic alopecia
- After 12 months of using topical minoxidil, 39% of subjects reported moderate to marked hair growth.
- Prognosis depends on treatment response.
• Alopecia areata
- Usually resolves within 3 years without treatment
- Recurrence common
• Traction alopecia
- Depends on behavior modification
• Tinea capitis
- Usually complete recovery
PATIENT MONITORING
With ketoconazole, monitor liver enzymes
REFERENCES
1. Ross EK. Management of hair loss. Dermatol Clin. 2005;23(2):227-243.
2. University of Texas at Austin School of Nursing, Family Nurse Practitioner Program. Recommendations to diagnose and treat adult hair loss disorders or alopecia in primary care settings (non pregnant female and male adults). 2004 May. 21 pages. NGC:003722 at www.guidelines.gov
3. Fiedler VC, Alaiti S. Treatment of alopecia areata. Dermatol Clin. 1996;14:733-738.
4. Habif TP. Hair Diseases: Clinical Dermatology, 4th ed. 2004.
5. Jackson EA. Hair disorders. Prim Care. 2000;27:319-332.
6. Rietschel RL. A simplified approach to the diagnosis of alopecia. Dermatol Clin. 1996;14:691-695.
7. Sperling LC. Hair and systemic disease. Dermatol Clin. 2001;19:711-726.
8. Whiting DA. Chronic telogen effluvium. Dermatol Clin. 1996;14:723-731.

ALDOSTERONISM, PRIMARY

2008-12-30T22:45:00.000-08:00

ALDOSTERONISM, PRIMARY - Mark C. Horattas, MD, FACS
BASICS
DESCRIPTION
• The clinical syndrome of excess secretion of aldosterone is classically manifested by hypertension, hypokalemia, and depressed plasma renin activity (patients often present as normokalemic).
• Unilateral aldosterone-producing adenoma (APA): Cured with unilateral adrenalectomy
• Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia: Not cured with surgery, medical management
• System(s) Affected: Endocrine/metabolic
• Synonym(s): Conn syndrome; Aldosteronoma; Hyperaldosteronism
ALERT
Pregnancy Considerations
Can be associated with toxemia during pregnancy or persistent hypertension following delivery. Treat hypertension with agents proven to be safe during pregnancy; avoid spironolactone and ACE inhibitors.
EPIDEMIOLOGY (1)[A]
Incidence
Involves 1% of the hypertensive population
Prevalence
• Usually diagnosed during 4th to 6th decades
• More common in women
RISK FACTORS
Genetics
Can be associated rarely with familial multiple endocrine neoplasia (MEN) syndromes.
ETIOLOGY
• Unilateral aldosterone-producing adenoma (APA)
• Idiopathic hyperaldosteronism (IHA)
• Other rare subtypes

DIAGNOSIS
(2)[A]
SIGNS AND SYMPTOMS
Physical Exam
• Usually asymptomatic
• Most patients are normokalemic.
• Marked hypokalemia may be associated with muscle weakness and cramping, intermittent paralysis, headaches, palpitations, polydipsia, polyuria, or nocturia.
• Mild to severe hypertension, one of the causes for secondary hypertension
• Funduscopy: Benign or grade 1-2
• Edema (rare)
• Hypokalemia (not required)
• Metabolic alkalosis
• Relative "hypernatremia"
• Impaired glucose tolerance
TESTS
• Screen for primary aldosteronism
- Patients with hypertension and spontaneous hypokalemia
- Patients with treatment-resistant hypertension
• Plasma aldosterone levels, plasma renin activity
• Special tests
- Aldosterone suppression test with either a high salt diet or saline infusion
- Spironolactone treatment trial
Lab
• Hypokalemia with inappropriate kaliuresis
• Insuppressible urine or plasma aldosterone levels
• Low ambulatory plasma renin activity
• High plasma aldosterone to renin ratio (>20 in ng/dL [>55 nmol/L] and ng/mL/h, respectively)
• Normal glucocorticoid excretion
• Drugs that may alter lab results: Diuretics, ACE inhibitors, spironolactone
• Disorders that may alter lab results: Malignant hypertension
Imaging
• Adrenal CT (preferred over MRI) with fine cuts
• Iodocholesterol (NP-59) scan with dexamethasone suppression
• Adrenal vein sampling (3)[A]
Diagnostic Procedures/Surgery (4)[A]
• Laparoscopic adrenalectomy if localized on CT scan
• Adrenal venous sampling for lateralization preoperatively if not localized by CT scan.
Pathological Findings
• Aldosteronoma usually a benign solitary adenoma.
• Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal (zona glomerulosa) hyperplasia
• Aldosterone-producing adrenocortical carcinoma rarely
DIFFERENTIAL DIAGNOSIS
• Diuretic use
• Renovascular hypertension
• Pheochromocytoma
• Renin-secreting tumor
• Malignant hypertension
• Congenital adrenal hyperplasia
• Deoxycorticosterone-producing tumor
• Exogenous mineralocorticoid
• High-dose glucocorticoid therapy
• Apparent mineralocorticoid excess syndrome (congenital or acquired due to licorice ingestion)
• Liddle syndrome
TREATMENT
STABILIZATION
• Appropriate health care
- Unilateral APA: Unilateral adrenalectomy
- Bilateral IHA: Chronic medical therapy
• Unilateral APA: Correct hypokalemia preoperatively with spironolactone
• Bilateral IHA: Low-sodium diet, regular isotonic exercise, maintenance of ideal body weight, tobacco avoidance, mineralocorticoid receptor antagonist, antihypertensive agent (e.g., calcium channel antagonist, ACE-inhibitor, low-dose thiazide diuretic)
Diet
Low sodium
MEDICATION (DRUGS)
• Potassium-sparing agent: Spironolactone (Aldactone) or amiloride (Midamor)
• Antihypertensive agent: Calcium channel antagonist, ACE inhibitor, angiotensin-II receptor antagonist, or low-dose thiazide diuretic
• Contraindications: Potassium-sparing agent and ACE inhibitors in renal failure, hyperkalemia, and pregnancy
• Precautions: Monitor serum potassium closely after any adjustment in potassium replacement or potassium-sparing agent.
• Significant possible interactions: Lithium and diuretics, NSAIDs with diuretics, and ACE inhibitors
SURGERY
The treatment of choice for patients with unilateral APA is adrenalectomy. Patients with bilateral IHA are treated medically.
FOLLOW-UP
PROGNOSIS
• Surgical removal of an APA results in a cure of hypertension in ~30-60% of the cases.
• Hypertension does not resolve immediately postoperatively, but rather over 1-4 months.
COMPLICATIONS
Cardiac arrhythmia associated with severe hypokalemia
PATIENT MONITORING
• BP checks
• Serum potassium check
• 24-hour urine aldosterone following surgery
REFERENCES
1. Clark OH, Duh QY. Textbook of Endocrine Surgery. Philadelphia; WB Saunders, 2005.
2. Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004;89:045 [PMID 15001583].
3. Young WF, Stanson AW, Thompson GB, et al. Role for adrenal venous sampling in primary aldosteronism. Surgery. 2004;136:1227 [PMID 15657580].
4. Mansmann G, Lau J, Balk E, et al. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev. 2004;25:309.

ALCOHOL USE DISORDERS

2008-12-30T06:46:00.000-08:00

ALCOHOL USE DISORDERS - Geninne Zinner, RNCS, ANP
BASICS
DESCRIPTION
• Any pattern of alcohol use causing significant physical, mental, or social dysfunction; key features are tolerance, withdrawal, and persistent use despite problems.
• Alcohol abuse: Maladaptive pattern of alcohol use manifested by 1 (or more) of
- Failure to fulfill obligations at work, school, or home
- Recurrent use in hazardous situations
- Recurrent alcohol-related legal problems
- Continued use despite related social or interpersonal problems
• Alcohol dependence: Maladaptive pattern of use manifested by 3 (or more) of the following
- Tolerance
- Withdrawal
- Using more than intended
- Persistent desire or attempts to cut down/stop
- Significant amount of time obtaining, using, or recovering from alcohol
- Social, occupational, or recreational activities sacrificed for alcohol use
- Continued use despite physical or psychological problems
• National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria for "at risk" drinking: Men >14 drinks a week, or >4 per occasion. Women: >7 drinks a week, or >3 per occasion.
• System(s) Affected: Nervous; Gastrointestinal
• Synonym(s): Alcoholism; Alcohol abuse; Alcohol dependence
ALERT
Geriatric Considerations
• Common in elderly; less likely to report problem. May exacerbate normal age-related cognitive deficits and disabilities.
• Multiple drug interactions
• Signs and symptoms may be different or attributed to chronic medical problem or dementia.
• Assessment tools may be inappropriate.
Pediatric Considerations
• Children of alcoholics at high risk
• In 2004, 28% of persons 12-20 years reported use in past month, 1 in 5 binge drink; binge drinkers are 7 more likely to report illicit drug use.
• Negative effect on maturation and development
• Early drinkers are 4 times more likely to develop a problem than those who begin >21.
• Depression, suicidal or disorderly behavior, family disruption, violence or destruction of property, poor school or work performance, sexual promiscuity, social immaturity, lack of interests, isolation, moodiness
Pregnancy Considerations
• Alcohol is teratogenic, especially during the 1st trimester; women should abstain during conception.
• 10-50% of children born to women who are heavy drinkers will have fetal alcohol syndrome.
• Women experience harmful effects at lower levels, and are less likely to report problems.
GENERAL PREVENTION
Counsel with family history and risk factors.
EPIDEMIOLOGY
• Predominant age: 18-25, but all ages affected
• Predominant sex: Male > Female (3:1)
Prevalence
• Lifetime prevalence: 13.6%
• 20% in primary care setting
• 48.2% of 21-year-olds in the US reported binge drinking in 2004.
RISK FACTORS
Family history, depression (40% with comorbid alcohol abuse), anxiety, other substance abuse, tobacco, male gender, low socioeconomic status, unemployment, peer/social approval, family dysfunction or trauma, PTSD, antisocial personality disorder, bipolar disorder, eating disorders, criminal involvement
Genetics
50-60% of risk is genetic.
PATHOPHYSIOLOGY
• Alcohol is a central nervous system depressant by facilitating -aminobutyric acid (GABA) inhibition and blocking N-methyl-D-aspartate receptors.
• Once tolerance has occurred, abrupt withdrawal results in hyperexcitability of these pathways.
ETIOLOGY
Multifactorial: Genetic, environment, psychosocial
ASSOCIATED CONDITIONS
• Cardiomyopathy
• Atrial fibrillation
• Hypertension
• PUD/gastritis
• Cirrhosis
• Fatty liver
• Cholelithiasis
• Hepatitis
• Diabetes mellitus
• Pancreatitis
• Malnutrition
• Upper GI malignancies
• Peripheral neuropathy
• Seizures
• Abuse
• Violence
• Trauma (falls, MVAs)

DIAGNOSIS
SIGNS AND SYMPTOMS
• Behavioral
- Anxiety, depression, insomnia;
- Visual, auditory, tactile hallucinations 12-72 hours after last drink
- Psychological and social dysfunction marital problems
- Social isolation/withdrawal
- Domestic violence
- Alcohol-related legal problems
- Repeated attempts to stop/reduce
- Loss of interest in nondrinking activities
- Employment problems (tardiness, absenteeism, decreased productivity, interpersonal problems, frequent job loss)
- Blackouts
- Complaints about alcohol-related behavior
- Frequent trauma, MVAs, ED visits.
• Physical
- Anorexia
- Nausea, vomiting
- Abdominal pain
- Palpitations
- Headache
- Impotence
- Menstrual irregularities
- Infertility
Physical Exam
• General: Fever, agitation, diaphoresis
• HEENT: Plethoric, rhinophyma, poor oral hygiene, oropharyngeal malignancies
• Cardiovascular: Hypertension, dilated cardiomyopathy, tachycardia
• Respiratory: Aspiration pneumonia
• Gastrointestinal: Stigmata of chronic liver disease, peptic ulcer disease, pancreatitis, esophageal malignancies, varices
• Genitourinary: Testicular atrophy
• Musculoskeletal: Unhealed fractures, myopathy, osteopenia, bone marrow suppression
• Neurologic: Tremors, cognitive deficits (e.g., memory impairment), peripheral neuropathy, Wernicke-Korsakoff syndrome, grand mal seizures 2-48 hours after last drink, delirium tremens (DTs) begin 48-72 hours after last drink
• Endocrine/metabolic: Hyperlipidemias, cushingoid appearance, gynecomastia
• Dermatologic: Burns (e.g., cigarettes), bruises, poor hygiene, palmar erythema, spider telangiectasias, caput medusa, jaundice
• Physical exam may be completely normal
• Withdrawal symptoms begin 4-12 hours after alcohol is stopped/reduced; peak in intensity on day 2 of abstinence; and are mostly resolved by 4th or 5th day
TESTS
• CAGE Questionnaire: (Cut down, Annoyed, Guilty, and Eye opener): More than 2 "yes" answers is 74-89% sensitive, 79-95% specific for alcohol use disorder; less sensitive for early problem drinking, or heavy drinking (1)[A]
• Alcohol Use Disorders Identification Test: 10 items, if >4: 70-92% sensitive (1)[A]
• "Had 5 or more drinks on any 1 occasion in last 3 months" sensitive screen for problem drinking
Lab
• Blood alcohol concentration
- >100 mg/dL in outpatient setting
- >150 mg/dL without obvious signs of intoxication
- >300 mg/dL at any time
• Levels suggestive if increased
- AST/ALT ratio >2.0
- -Glutamyl transferase (GGT)
- Mean corpuscular volume
- Prothrombin time
- Uric acid
- Triglycerides
- Cholesterol (total)
• Often decreased
- Calcium, magnesium, potassium, phosphorus
- Blood urea nitrogen (BUN)
- Hemoglobin, hematocrit
- Platelet count
- Serum protein, albumin
Imaging
• Radiograph: Multiple old rib fractures
• CT scan, MRI of brain: Cortical atrophy, lesions in thalamic nucleus and basal forebrain
Pathological Findings
• Liver: Inflammation or fatty infiltration (alcoholic hepatitis), periportal fibrosis (alcoholic cirrhosis occurs in only 10-20% of alcoholics)
• Gastric mucosa: Inflammation, ulceration
• Pancreas: Inflammation, liquefaction necrosis
• Heart: Dilated cardiomyopathy
• Immune system: Decreased granulocytes
• Endocrine organs: Elevated cortisol levels, testicular atrophy, decreased female hormones
• Brain: Cortical atrophy, enlarged ventricles
DIFFERENTIAL DIAGNOSIS
• Other substance use disorders
• Depression
• Dementia
• Cerebellar ataxia
• CVA
• Benign essential tremor
• Seizure disorder
• Hypoglycemia
• Diabetic ketoacidosis
• Viral hepatitis
TREATMENT
PRE-HOSPITAL
• Assess medical and psychiatric condition.
• Assess severity of withdrawal.
STABILIZATION
• Airways, breathing, circulation
• Short-acting benzodiazepine for seizure
• Correct electrolyte imbalances, acidosis
GENERAL MEASURES
• Brief interventions by primary care physicians are highly effective for problem drinking (1)[A].
• Involve family, if feasible.
• Treat comorbid problems (sleep, anxiety, etc.); use caution if prescribing medications with cross-tolerance to alcohol (benzodiazepine).
Activity
Fall preventions or restrictions if delirious
Nursing
• Frequent vital signs during acute withdrawal
• Clinical Institute Withdrawal Assessment Scale for Alcohol (CIWA-Ar) very helpful (2,3)[A].
IV Fluids
Maintain fluids during withdrawal.
MEDICATION (DRUGS)
First Line
• Symptom-triggered regimens (benzodiazepine given only when CIWA-Ar score > 8) result in less total medication given and shorter duration of treatment than fixed-dose regimens (2,3)[A].
• In fixed-dose regimens, 1st dose of benzodiazepine should achieve sedation without respiratory compromise; drugs then are tapered daily as long as withdrawal symptoms are stable; CIWA-Ar is often used to guide dosing.
• Benzodiazepines reduce incidence of DTs and seizures (2,3)[A].
- Chlordiazepoxide 50-100 mg PO/IM q6-8h, then taper (2-4)[A]
- Diazepam 5-20 mg q6-8h (2-4)[A]
- Lorazepam 1-4 mg q2-6h (2,3)[A]; in elderly, severe liver disease, or IV drip
- Phenobarbital 60-120 mg q6-8h (4)[B] may be safer during pregnancy.
- Carbamazepine 200 mg PO q.i.d., then taper over 5-7 days (efficacious for mild-moderate withdrawal, and is less sedating) (2)[A].
• Adjuncts to detoxification
- -Blockers for tachycardia or comorbid coronary artery disease (3)[B]
- Clonidine 0.1-0.2 mg PO t.i.d. for autonomic hyperactivity (3,4)[C]
- Antipsychotics for psychosis, agitation; haloperidol lowers seizure threshold (3)[C]
• Adjuncts to rehabilitation
- Naltrexone 50-100 mg PO daily, or 380 mg IM once every 4 weeks: Opiate antagonist reduces craving and chance relapse (5)[A].
- Acamprosate (Campral) 666 mg PO t.i.d. beginning after completion of withdrawal; reduces relapse of drinking (5)[A]
- Topiramate (Topamax) 25-300 mg PO daily or divided b.i.d.; enhances abstinence (3)[B]
• Supplements to all
- Thiamine 100 mg daily (1st dose IV prior to glucose to avoid Wernicke encephalopathy)
- Folic acid 1 mg daily
- Multivitamin daily
- Magnesium sulfate 1 g IM/IV q4-6h (if history of DTs or seizure) (2)[C]
• Contraindications
- Naltrexone: Pregnancy, hepatitis, hepatic failure. Monitor liver function tests.
• Precautions: Organic pain, organic brain syndromes
• Significant possible interactions: Alcohol, sedatives, hypnotics
Second Line
• Anticonvulsants gabapentin (Neurontin) and vigabatrin (Sabril) studied for detoxification (3)[B]
• Disulfiram 250-500 mg PO daily: Unproven efficacy; may provide psychologic deterrent
• Selective serotonin reuptake inhibitors (SSRIs) may be beneficial if comorbid depression exists.
FOLLOW-UP
DISPOSITION
Admission Criteria
Severe withdrawal symptoms (CIWA-Ar >14), prior DTs, withdrawal seizures, suicidal ideation or psychiatric symptoms, obstacles to follow-up, pregnancy, unstable living situation
Issues for Referral
Addiction specialist: 12-step or long-term program
PROGNOSIS
• Chronic relapsing disease; mortality rate > twice general population, death 10-15 years earlier
• Abstinence benefits survival, mental health, family, employment
• 12-step programs, cognitive-behavior and motivational therapies are effective during 1st year following treatment (1)[B].
COMPLICATIONS
• Cirrhosis
• GI malignancies
• Neuropathy
• Dementia
• Wernicke-Korsakoff syndrome
• CVA
• Ketoacidosis
• Infection
• Relapse
• Depression
• Suicide
• Trauma
PATIENT MONITORING
• Outpatient detoxification: Daily visits
• Early outpatient rehabilitation: Weekly visits
• Detoxification alone is not sufficient.
REFERENCES
1. Enoch MA, Goldman D. Problem drinking and alcoholism: Diagnosis and treatment. Amer Fam Phys. 2002;65:441-448.
2. Asplund CA, Aaronson JW, Aaronson HE. Three regimens for alcohol withdrawal and detoxification. J Fam Pract. 2004;53:545-554.
3. Bayard M, McIntyre J, Hill KR, et al. Alcohol withdrawal syndrome. Amer Fam Phys. 2004;69(pt 6):1443-1450.
4. Kosten TR, O'Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348:1786-1795.
5. Saitz R. Clinical practice. Unhealthy alcohol use. N Engl J Med. 2005;352-396.
6. Williams SH. Medications for treating alcohol dependence. Amer Fam Phys. 2005;72(pt 9):1775-1780.
ADDITIONAL READING
• Substance Abuse and Mental Health Services Administration. (NSDUH series H-27, DHHS Publication No. SMA 05-4061). 2005. (http://oas.samhsa.gov/prevalence.htm)
• National Institute on Alcohol Abuse and Alcoholism: (NIH Publication No. 00-1583). 2000. (http://pubs.niaaa.nih.gov/publications/10report/intro.pdf)
• National Council on Alcoholism and Drug Dependence. NCADD Fact Sheet. Available online: ncadd.org/pubs/fsproblems.html

ADENOVIRUS INFECTIONS

2008-12-30T06:42:00.000-08:00

ADENOVIRUS INFECTIONS - Ronald L. Malm, DO
BASICS
DESCRIPTION
Usually self-limited febrile illnesses characterized by inflammation of conjunctivae and the respiratory tract. Adenovirus infections occur in epidemic and endemic situations.
• Common types
- Acute febrile respiratory illness, affecting primarily children
- Acute respiratory disease, affecting adults
- Viral pneumonia, affecting children and adults
- Acute pharyngoconjunctival fever, affecting children, particularly after summer swimming
- Acute follicular conjunctivitis, affecting all ages
- Epidemic keratoconjunctivitis, affecting adults
- Intestinal infections leading to enteritis, mesenteric adenitis, and intussusception
• Conjunctivitis, sometimes called pink eye
• System(s) Affected: Cardiovascular; Gastrointestinal; Hemic/Lymphatic/Immunologic; Musculoskeletal; Nervous; Pulmonary; Renal/Urologic
ALERT
Geriatric Considerations
Complications more likely
Pediatric Considerations
Viral pneumonia in infants may be fatal.
GENERAL PREVENTION
• Live types 4 and 7 adenovirus vaccine orally in enteric-coated capsules reduces incidence of acute respiratory disease.
• Frequent hand washing among office personnel and family members
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
• Very common infection, estimated at 2-5% of all respiratory infections
• More common in infants and children
RISK FACTORS
• Large number of people gathered in a small area (e.g., military recruits, college students at the beginning of the school year, day care centers, community swimming pools, etc.)
• Immunocompromised at risk for severe disease
ETIOLOGY
• Adenovirus (DNA viruses 60-90 nm in size with 47 known serotypes; three types cause gastroenteritis); difficult to eliminate from skin and environmental surfaces
• Different serotypes have different epidemiologies.
• Most common known pathogens
- Types 1, 2, 3, 5, and 7 cause respiratory illness.
- Type 3 causes pharyngoconjunctival fever.
- Types 4, 7, and 21 cause acute respiratory disease.
- Several other types may cause epidemic keratoconjunctivitis.
ASSOCIATED CONDITIONS
• Hemorrhagic cystitis (can be caused by adenovirus)
• Viral enteritis
• Intussusception and mesenteric adenitis

DIAGNOSIS
SIGNS AND SYMPTOMS
History
Depends on type (see "Differential Diagnosis"). Common signs and symptoms with most respiratory forms
• Headache
• Malaise
• Sore throat
• Cough
• Fever (moderate to high)
• Vomiting
• Diarrhea
Physical Exam
• Mucosa exhibits patches of white exudates
• Cervical adenitis
TESTS
Cultures and serologic studies, if appropriate
Lab
• Viral cultures from respiratory, ocular, or fecal sources can establish diagnosis:
- Pharyngeal isolate suggests recent infection.
• Antigen detection in stool for enteric serotypes is available.
• Serologic procedures such as complement fixation with a fourfold rise in serum antibody titer identify recent adenoviral infection.
Imaging
Radiographs: Bronchopneumonia in severe respiratory infections
Diagnostic Procedures/Surgery
Biopsy (lung or other) may be needed in severe or unusual cases
Pathological Findings
• Varies with each virus:
- Severe pneumonia may be reflected by extensive intranuclear inclusions.
• Bronchiolitis obliterans may occur.
DIFFERENTIAL DIAGNOSIS
Early diagnosis depends on clinical evaluation. The following are the primary characteristics of the major adenovirus infections:
• Acute febrile respiratory illness
- Nonspecific coldlike symptoms, similar to other viral respiratory illnesses (e.g., fever, pharyngitis, tracheitis, bronchitis, pneumonitis)
- Mostly in children
- Incubation period 2-5 days
- May be pertussislike syndrome (rarely)
• Acute respiratory disease
- Malaise, fever, chills, headache, pharyngitis, hoarseness, dry cough
- Fever lasts 2-4 days
- Illness subsides in 10-14 days
• Viral pneumonia
- Sudden onset of high fever, rapid infection of upper and lower respiratory tracts, skin rash, diarrhea
- Occurs in children aged a few days up to 3 years
- Common; severe illness occurs in subset
• Acute pharyngoconjunctival fever
- Spiking fever lasting several days, headache, pharyngitis, conjunctivitis, rhinitis, cervical adenitis
- Conjunctivitis, usually unilateral
- Subsides in 1 week
• Epidemic keratoconjunctivitis
- Usually unilateral onset of ocular redness and edema, periorbital edema, periorbital swelling, local discomfort suggestive of foreign body
- Lasts 3-4 weeks
TREATMENT
GENERAL MEASURES
• Treatment is supportive and symptomatic.
• Infections are usually benign and of short duration.
Diet
No special diet
Activity
Rest during febrile phases
SPECIAL THERAPY
Complementary and Alternative Medicine
Echinacea has not been shown to be better than placebo for treatment of viral upper respiratory infections. [A]
MEDICATION (DRUGS)
• Acetaminophen, 10-15 mg/kg/dose PO, for analgesia (avoid aspirin)
• Topical corticosteroids for conjunctivitis (after consulting an ophthalmologist)
• Cough suppressants and/or expectorants
• Antihistamine/decongestant combos may decrease cough. [B]
FOLLOW-UP
DISPOSITION
Admission Criteria
Severely ill infants or those with epidemic keratoconjunctivitis or infants with severe pneumonia
• Contact and droplet precautions during a hospitalization are indicated.
PROGNOSIS
• Self-limited, usually without sequelae
• Severe illness and death in very young and in immunocompromised hosts
COMPLICATIONS
Few if any recognizable long-term problems
PATIENT MONITORING
For severe infantile pneumonia and conjunctivitis, daily physical exam until well
REFERENCES
1. Barrett BP, Brown RL, Locken K, Maberry R, Bobula JA, D'Alessio D. Treatment of the common cold with unrefined echinacea. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2002;137(12):939-946.
2. Pratter MR. Cough and the Common Cold, ACCP Evidence-Based Clinical Practice Guidelines Chest. 2006;129:72S-74S
3. Fahey T, Smucny J, Becker L, Glazier R. Antibiotics for acute bronchitis. The Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD000245. DOI: 10.1002/14651858. CD000245.pub2.
4. Morris P, Leach A. Antibiotics for persistent nasal discharge (rhinosinusitis) in children. The Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD001094. DOI: 10.1002/14651858. CD001094.
5. Spurling GKP, Del Mar CB, Dooley L, Foxlee R. Delayed antibiotics for symptoms and complications of respiratory infections. The Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD004417. DOI: 10.1002/14651858.CD004417.pub2.

ADDISON DISEASE

2008-12-30T06:40:00.000-08:00

ADDISON DISEASE - Rick Kellerman, MD; Mark Gerstberger, DO
BASICS
DESCRIPTION
• Adrenal hypofunction from primary disease (partial or complete T-cell-mediated destruction of adrenal cells) of the adrenal gland with inadequate secretion of glucocorticoids and mineralocorticoids
• An autoimmune process is the most common cause (80% of the cases), followed by tuberculosis; AIDS is becoming a more frequent cause.
• Addison disease (primary adrenocortical insufficiency) is differentiated from secondary (pituitary failure) and tertiary (hypothalamic failure) causes of adrenocortical insufficiency (see Differential Diagnosis). Mineralocorticoid function usually remains intact in secondary and tertiary adrenocorticoid insufficiency
• Addisonian (adrenal) crisis: Acute complication of adrenal insufficiency (circulatory collapse, dehydration, hypotension, nausea, vomiting, hypoglycemia); usually precipitated by an acute physiologic stressor(s) such as surgery, illness, exacerbation of comorbid process, and/or acute withdrawal of long-term corticosteroid therapy
• System(s) Affected: Endocrine/metabolic
• Synonym(s): Adrenocortical insufficiency; Waterhouse-Frederickson syndrome (adrenal crisis); Corticoadrenal insufficiency; Primary adrenocortical insufficiency
ALERT
Geriatric Considerations
Acute adrenal crisis is more likely in geriatric patients.
Pediatric Considerations
• Hydrocortisone and fludrocortisone doses are lower than adults
• More difficult to diagnose
• Occurs in siblings
GENERAL PREVENTION
• No preventive measures known for Addison disease.
• Prevention of complications
- Anticipate adrenal crisis and treat before symptoms begin.
- Elective surgical procedures require upward adjustment in steroid dose.
EPIDEMIOLOGY
• Predominant age: All ages; usually 3rd to fifth decade
• Predominant sex: Females > Males (slight)
Incidence
0.6:100,000
Prevalence
4:100,000
RISK FACTORS
• Family history of autoimmune adrenal insufficiency. ~40% of patients have a 1st- or 2nd-degree relative with associated disorders.
• Chronic steroid use, then experiencing severe infection, trauma, or surgical procedures
Genetics
Familial glucocorticoid insufficiency may have a recessive pattern; adrenomyeloneuropathy is X-linked. Frequent association with other autoimmune disorders. Increased risk with cytotoxic T lymphocyte antigen 4 (CTLA-4)
ETIOLOGY
• Autoimmune adrenal insufficiency (80% of cases in the U.S.)
• Tuberculosis (most common infectious cause worldwide)
• HIV (most common infectious cause in the U.S.)
• Waterhouse-Fredrickson syndrome (disseminated adrenal infection and subsequent infarction; meningococcemia most common; pseudomonas aeruginosa in children; CMV, cryptococcus, MAC in immunosuppressed, AIDS)
• Fungal disease (histoplasmosis, blastomycosis, coccidioidomycosis)
• Bilateral adrenal hemorrhage and infarction (anticoagulants; 50% are in the therapeutic range at the time of the hemorrhage)
• Antiphospholipid syndrome
• Metastatic (lung, breast, kidney, colon, melanoma), lymphoma, Kaposi sarcoma (tumor must destroy 90% of gland to produce hypofunction)
• Drugs (ketoconazole, etomidate)
• Shock
• Surgical adrenalectomy
• Radiation therapy
• Sarcoidosis
• Hemochromatosis
• Amyloidosis
• Adrenoleukodystrophy
• Adrenomyelodystrophy
• Polyglandular autoimmune endocrine syndromes
- APS I (autoimmune polyglandular syndrome 1): Childhood onset (HLA-DR not associated), single gene mutation in APECED gene (APECED: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy)
- APS II (autoimmune polyglandular syndrome II): Schmidt syndrome (50% of patients with Addison disease have Schmidt syndrome), adult onset (HLA-DR associated), adrenal failure with type I diabetes mellitus, and/or autoimmune thyroid disease (Hashimoto or Graves)
- APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy): Autosomal recessive, any 2 of chronic mucocutaneous candidiasis, hypothyroidism or Addison disease
- XPID (X-linked polyendocrinopathy, immune dysfunction, diarrhea): Rare; neonatal death
• Congenital (enzyme defects, hypoplasia, familial glucocorticoid insufficiency)
• Idiopathic
ASSOCIATED CONDITIONS
Diabetes mellitus, Grave disease, Hashimoto thyroiditis, Hypoparathyroidism, Hypercalcemia, Ovarian failure, Pernicious anemia, Myasthenia gravis, Vitiligo, Chronic moniliasis, Sarcoidosis, Sjogren syndrome, Chronic active hepatitis, Schmidt syndrome (multiple endocrine deficiency syndrome), Adrenoleukodystrophy

DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Weakness, fatigue, tiredness
• Dizziness
• Anorexia, nausea, vomiting
• Abdominal pain
• Chronic diarrhea
• Depression (60-80% of patients)
• Decreased cold tolerance
• Salt craving
Physical Exam
• Weight loss
• Low BP, orthostatic hypotension
• Increased pigmentation (extensor surfaces, hand creases, dental-gingival margins, buccal and vaginal mucosa, lips, areola, pressure points, scars, "tanning," freckles)
• Vitiligo
• Hair loss in females
TESTS
• Basal plasma cortisol and ACTH (low cortisol and high ACTH indicative of Addison disease)
• Rapid ACTH stimulation test: Cosyntropin 0.25 mg IV, measure preinjection and baseline, 30-, and 60-minute postinjection cortisol levels. (Patients with Addison disease have low to normal values that do not rise.)
• Metapyrone test
• Insulin-induced hypoglycemia test
• CRH may help distinguish secondary from tertiary adrenal insufficiency.
• Autoantibody tests: 21-Hydroxylase (most common and specific), 17-hydroxylase, 17-alfa-hydroxylase (may not be associated), and adrenomedullin
Lab
• Low serum sodium
• Elevated serum potassium
• Elevated BUN, creatinine
• Elevated serum calcium
• Hypoglycemia when fasted
• Metabolic acidosis
• Low cortisol level (between 8 and 9 AM)
• Elevated ACTH level
• Moderate neutropenia
• Eosinophilia
• Relative lymphocytosis
• Anemia, normochromic, normocytic
• Adrenal-cortex autoantibody (ACA/21-hydroxylase)
• Low aldosterone levels
• TSH: Repeat when condition has stabilized
- Thyroid hormone levels may normalize with the treatment of Addison disease.
• Drugs that may alter lab results: Digitalis.
• Disorders that may alter lab results: Diabetes mellitus
Imaging
• Abdominal CT scan
- Small adrenal glands in autoimmune adrenalitis
- Enlarged adrenal glands in infiltrative and hemorrhagic disorders
• Abdominal radiograph may show adrenal calcifications.
• CXR may show small heart size, and/or calcification of cartilage.
Diagnostic Procedures/Surgery
CT guided fine-needle biopsy of adrenal masses may be helpful.
Pathological Findings
• Atrophic adrenals in autoimmune adrenalitis
• Infiltrative and hemorrhagic disorders produce enlargement with destruction of the entire gland.
DIFFERENTIAL DIAGNOSIS
• Secondary adrenocortical insufficiency (pituitary failure)
- Withdrawal of long-term corticosteroid use: Adrenal insufficiency from hypothalamic-pituitary axis depression from long-term corticosteroid use is much more common than Addison disease.
- Sheehan syndrome (postpartum necrosis of pituitary)
- Empty sella syndrome
- Surgical excision of pituitary
- Radiation to pituitary
- Pituitary adenomas, carcinomas (rare), craniopharyngiomas
- Infiltrative disorders of pituitary (sarcoidosis, hemochromatosis, amyloidosis, histiocytosis X)
- Megestrol
• Tertiary adrenocortical insufficiency (hypothalamic failure)
- Pituitary stalk transection
- Trauma
- Disruption of production of corticotropic releasing factor (CRF)
- Hypothalamic tumors
• Myopathies
• Secretion of inappropriate antidiuretic hormone (SIADH)
• Heavy metal ingestion
• Severe nutritional deficiencies
• Sprue syndrome
• Hyperparathyroidism
• Neurofibromatosis
• Peutz-Jeghers syndrome
• Porphyria cutanea tarda
• Salt-losing nephritis
• Bronchogenic carcinoma
• Anorexia nervosa
• Other causes of hypoglycemia
• Depression
TREATMENT
STABILIZATION
• Outpatient
• Inpatient during adrenal crisis
GENERAL MEASURES
• Treatment for adrenal insufficiency is with glucocorticoid and mineralocorticoid replacement.
- The 5 S's of management of adrenal crisis: Salt, sugar, steroids, support, and search for a precipitating illnessusually infection, trauma, recent surgery, or not taking prescribed replacement therapy.
• Appropriate treatment for underlying cause
Diet
Diet to maintains water, sodium, and potassium balances.
Activity
As tolerated
MEDICATION (DRUGS)
First Line
• Chronic adrenal insufficiency
- Hydrocortisone 15-20 mg PO each morning on rising, and 10 mg at 4-5 PM each afternoon is the usual dosage (dosage may vary and is usually less in children's).
- Fludrocortisone 0.05-0.2 mg PO once daily plus
- Dehydroepiandrosterone 25-50 mg PO once daily (monitor lipid profile, breast or prostate cancer)
- May require salt supplementation
• Acute adrenal insufficiency
- Hydrocortisone 100 mg IV followed by 10 mg/h infusion
- IV glucose, saline, and plasma expanders
- Fludrocortisone 0.05 mg/d
• Acute illnesses (fever, stress, minor trauma):
- Double the patient's usual steroid dose; taper the dose gradually over a week or more, and monitor VS and serum sodium.
• Supplement for surgical procedures: Administer 25-150 mg hydrocortisone or 5-30 mg methylprednisolone IV on the day of the procedure in addition to maintenance therapy. Taper gradually to the usual dose over 1-2 days.
• Precautions
- Patients with hepatic disease may need a reduced dose of steroids.
- Excessive corticosteroid doses or excessive duration of supplemental treatment of those who are acutely ill or undergoing surgery may increase the mortality rate.
- Rifampin, phenytoin, and barbiturates may precipitate adrenal insufficiency in Addisonian patients by inducing steroid-metabolizing liver enzymes.
- Patients on these drugs may require higher doses of corticosteroid due to increased steroid metabolism.
- Refer to manufacturer's literature for other precautions
- Significant possible interactions: Refer to manufacturer's literature
Second Line
Prednisone 5 mg in the morning and 2.5 mg at night plus fludrocortisone, and DHEA; dexamethasone 0.5 mg in the morning plus fludrocortisone plus DHEA
ALERT
Geriatric Considerations
Elderly should have a slightly reduced dose.
FOLLOW-UP
PROGNOSIS
• Requires lifetime treatment
• Good outlook with appropriate treatment
• With adequate replacement therapy, life expectancy approximates normal.
• Without treatment, the disease is 100% lethal.
COMPLICATIONS
• Hyperpyrexia
• Psychotic reactions
• Complications from underlying disease
• Oversteroid or understeroid treatment
• Hyperkalemic paralysis (rare)
• Addisonian crisis
PATIENT MONITORING
• Verify adequacy of therapy: Normal BP, serum electrolytes normal, normal plasma renin, improvement of appetite and strength, increase in heart size to normal, and normal fasting blood glucose level
• Lifelong medical supervision for signs of adequate therapy and avoidance of overdose
REFERENCES
1. http://www.utdol.com/utd/content/topic.do?topicKey= adrenal/abstract.do?topicKey=adrenal/4314refNum=12
2. King MS. Adrenal insufficiency: An uncommon cause of fatigue. J Am Board Fam Pract. 1999;12:386-390. (C)
3. Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency [see comments]. N Engl J Med. 1999;341:1013-1020. (A)

ACOUSTIC NEUROMA

2008-12-30T06:38:00.000-08:00

ACOUSTIC NEUROMA - Sam Kim, MD, MBBS, MedSc; Phillip Chang, MD
BASICS
DESCRIPTION
• Slow-growing benign Schwannoma, most often arising from the vestibular division of 8th cranial nerve
• Originates from Schwann cells of the nerve sheath
• Usually arise in the internal auditory canal near the cerebellopontine angle
• Most are unilateral; bilateral only seen in Neurofibromatos type II
EPIDEMIOLOGY
• 6-10% of all intracranial tumors
• 80-90% of cerebellopontine angle tumors
• 95% of cases are unilateral
• Present most commonly in the 5th-6th decade
• Female predominance
• Bilateral acoustic neuroma occurring in Neurofibromatosis II present before age of 30
Incidence
• 1/100,000 per year
• Asymptomatic lesions may be more common
Prevalence
3,000 diagnosed annually in the US
RISK FACTORS
Unknown
Genetics
• Unknown for unilateral acoustic neuroma
• Neurofibromatosis type II: Bilateral ANs
- Autosomal domiant
- Gene located on chromosome 22q1
PATHOPHYSIOLOGY
Exerts pressure on the surrounding structures
• Compression of acoustic and facial nerve when within internal acoustic canal
• Compression of brainstem, 4th ventricle and trigeminal nerve when at the cerebellar pontine angle
ETIOLOGY
Unknown
ASSOCIATED CONDITIONS
• Neurofibromatosis type II
• Pregnancy may accelerate the growth of the tumor

DIAGNOSIS
SIGNS AND SYMPTOMS
• Common
- Sensorineural hearing loss (unilateral)
- Tinnitus
- Balance problems are common, but vertigo is less common.
• Less common
- Weakness/loss of facial muscle functions
- Headache with hydrocephalus and increased intracranial pressure
- Trigeminal nerve involvement when tumor is large and compressing on CN V
- Ataxia due to cerebellar or brainstem compression from very large tumor
History
• Hearing loss is often progressive
• Loss of speech discrimination
Physical Exam
• Examination with otoscope to exclude other causes of hearing loss (e.g., middle ear effusion, infection, wax, cholesteatoma or tympanic membrane rupture)
• Detailed neurological examination concentrating on the cranial nerves
• Weber and Rinne tests to confirm sensorineural hearing loss
• Evaluation of the contralateral ear in patients 30 years; suspect Neurofibromatosis type II
TESTS
• Pure-tone and speech audiometry (asymmetrical, high-frequency sensorineural hearing loss)
• Speech discrimination
• Stacked auditory brainstem response (ABR): 95% sensitivity and 88% specificity (1). Can detect tumors 1 cm
• Standard ABR: Can only detect tumors >1 cm.
Imaging
• MRI with gadolinium: Gold standard
- 100% specificity
- Detects tumors starting at 2 mm
- Tumor has marked enhancement with Gadolinium
• Noncontrast T2-weighted fast spin-echo MRI:
- 98% specificity
- Cheaper than MRI with gadolinium
• CT
- detect tumors as small as 1 cm
- Up to 37% false negatives
- Provides good information of surrounding bony structures of the tumor
Pathological Findings
• Well demarcated and encapsulated mass attached to neural structures without direct invasion
• Can be dense or cystic
• Microscopic: Densely packed spindle cells (Schwann cells) mixed in with myxoid and collagenous matrix
- Zones of alternatively dense and sparse areas of Antoni A and B
DIFFERENTIAL DIAGNOSIS
• Cerebellopontine lesions
- Meningioma
- Glioma
- Facial nerve Schwannoma
- Epidermoid
- Hemangioma
- Arachnoid cyst
• Sensorineural hearing loss
- Meniere's disease
- Ototoxicity
- Presbycusis
- Cerebellar pathology
TREATMENT
SPECIAL THERAPY
Conservative management:
• Suitable for elderly patients contraindicated to surgery and radiotherapy
• Up to 57% of acoustic neuromas may show no growth (2)[A]
• Average growth rate is 1.9 mm per year (2)[A]
• Up to 20% of patients may eventually fail conservative management.
Radiotherapy
Stereotactic radiosurgery
• Gamma knife stereotactic radiosurgery
- Performed on an outpatient basis
- Alternative for those with smaller tumor (3 cm) or contraindicated to microsurgery
- Have shown to suppress tumor growth and provide good tumor control (3)[B]
- Complications include trigeminal and/or facial nerve neuropathy from radiation damage.
• Fractionated stereotactic radiosurgery
- Conformal radiation delivers a higher dose radiation within the tumor and less damage to surrounding healthy tissue.
- Requires multiple treatment
MEDICATION (DRUGS)
Chemotherapy has not yet been explored sufficiently.
SURGERY
• Recommended definitive treatment (A)
• Lowest rate of recurrence, with up to 97.5% complete tumor removal (4)[A]
• Intraoperative facial nerve monitoring is generally used.
• 3 standard approaches
- Retromastoid/retrosigmoid: For any size
- Middle cranial fossa: For small tumors with aim of preserving hearing
- Translabirinthe: For larger tumors. Hearing not preserved. Completely exposes the distal internal auditory canal
• Surgical complications
- Hearing loss
- CSF leakage
- Facial nerve injury
- Headache
- Meningitis
FOLLOW-UP
COMPLICATIONS
Due to pressure effect of a large tumor
• Cranial nerve compression
• Hydrocephalus
• Brainstem compression
• Cerebellar tonsil herniation
REFERENCES
1. Don M, et al.The stacked ABR: a sensitive and specific screening tool for detecting small acoustic tumors. Audiol Neurootol. 2005;274-290.
2. Smouha EE, et al. Conservative management of acoustic neuroma: A meta-analysis and proposed treatment algorithm. Laryngoscope. 2005;450-454.
3. Lunsford LD, Niranjan A, Flickinger JC, et al. Radiosurgery of vestibular Schwannomas: Summary of experience in 829 cases. J Neurosurg. 2005;102 Suppl:195.
4. Kaylie DM, et al. A meta-analysis comparing outcomes of microsurgery and gamma knife radiosurgery. Laryngoscope. 2000;1850-1856.

ACNE VULGARIS

2008-12-30T06:36:00.000-08:00

ACNE VULGARIS - Katrina Miller, MD
BASICS
DESCRIPTION
• Acne vulgaris is a disorder of the pilosebaceous units (PSU), caused by androgen-mediated hyperkeratinization and increased sebum production, resulting in plugging of the follicles and formation of comedones. When further inflammation occurs, lesions include papules, inflammatory pustules, nodules, and scarring.
• System(s) Affected: Skin/exocrine
ALERT
Geriatric Considerations
Favre-Racouchot syndrome
Isotretinoin is a teratogenic; Pregnancy Class X
Pregnancy Considerations
• May result in a flare, or remission, of acne
• Erythromycin can be used in pregnancy; use topical agents when possible
• Avoid topical tretinoin, although no good evidence exists that its use is teratogenic.
• Contraindicated: Isotretinoin, tazarotene, tetracycline, doxycycline, minocycline
Pediatric Considerations
• Neonatal acne
• Infantile acne: Increased risk for severe teenage acne vulgaris.
• Rare in ages 1-7 years
- Check for hyperandrogenemia of adrenal or ovarian origin
- Do not use tetracyclines 8 years of age
• Adolescent acne
- Often very significant to adolescent patient
- Often an "entry ticket" for advice on lifestyle, contraception, physiology, etc.
EPIDEMIOLOGY
• Predominant age
- Primarily early to late puberty, may persist into 3rd to 4th decades
- Affected ages: All
• Predominant sex
- Male > Female (adolescence)
- Female > Male (adult)
Prevalence
• 17-50 million in the U.S. Varies geographically.
• Nearly 100% of adolescents affected. A smaller percentage will seek medical advice.
• 8% of 25-34 year olds, 3% of 35-44 year olds
RISK FACTORS
• Adolescence
• Increased endogenous androgenic effect
• Androgenic steroids (e.g., steroid abuse, some birth control pills)
• Possibly stress
• Oily cosmetics: Cleansing creams, moisturizers, and oil-based foundations; pomade
• Rubbing or occluding skin surface (e.g., sports equipment such as helmets and shoulder pads), telephone or hands against the skin
• Drugs
- Androgens and androgenic stimulants
- Anabolic steroids
- Systemic corticosteroids
- Long-acting progestins
- Lithium, phenytoin, isoniazid, phenobarbital, ethionamide, azathioprine, disulfiram, cyclosporine, quinine, thiourea, and thiouracil
• Virilization disorders: PCOS
• Hot, humid climate
Genetics
• Familial association.
• If a family history exists, the acne may be more severe and occur earlier.
PATHOPHYSIOLOGY
• Androgens (testosterone and DHEA)
- Stimulate sebum production and proliferation of keratinocytes in hair follicles
• Keratin plug obstructs follicle os, causing sebum accumulation and follicular distention
• Propionibacterium acnes, an anaerobe, colonizes and proliferates in the plugged follicle.
- P. acnes promotes chemotactic factors and proinflammatory mediators, causing inflammation of follicle and dermis.
ETIOLOGY
Androgens, inflammation, and P. acnes
ASSOCIATED CONDITIONS
• Acne fulminans
• Pyoderma faciale
• Acne conglobata
• Hidradenitis suppurativa
• Pomade acne
• SAPHO syndrome: Synovitis, acne, pustulosis, hyperostosis, osteitis
• PAPA syndrome: Pyogenic sterile arthritis, pyoderma gangrenosum, cystic acne
• Dark-skinned patients: 50% keloidal scarring and 50% acne hyperpigmented macules (AHMs)

DIAGNOSIS
SIGNS AND SYMPTOMS
• Closed comedones (whiteheads)
• Open comedones (blackheads)
• Nodules or papules
• Pustules ("cysts")
• Scars: Ice pick, rolling, boxcar, atrophic macules, hypertrophic, depressed, sinus tracts
• Most common areas affected are: face, chest, back, and upper arms (areas of greatest concentration of sebaceous glands)
• Factors influencing symptomatology
- Males later onset, greater severity
- Females may worsen immediately prior to menses
• Grading system (American Academy of Dermatology, 1990)
- Mild: Few papules/pustules; no nodules
- Moderate: Some papules/pustules; few nodules
- Severe: Numerous papules/pustules; many nodules
- Very severe: Acne conglobata, acne fulminans, acne inversa
History
Duration, medications, cleansing products, stress, smoking, exposures, family history
Physical Exam
Type of lesions, number, location
TESTS
Lab
Testosterone, dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) measure in rare cases when acne arises de novo in previously unaffected adult. High levels or LH:FSH ratio >2.5 suggests PCOS.
Pathological Findings
• Oiliness, thickening of the skin
• Hypertrophy of the sebaceous glands
• Perifolliculitis
• Scarring
DIFFERENTIAL DIAGNOSIS
• Folliculitis
• Acne (rosacea, cosmetica, steroid induced)
• Perioral dermatitis
• Chloracne
• Pseudofolliculitis barbae
• Drug eruption
• Verruca vulgaris and plana
• Keratosis pilaris
• Molluscum contagiosum
TREATMENT
GENERAL MEASURES
• Therapy goals
- Lessen physical discomfort
- Minimize scarring
- Improve appearance
- Avoid adverse psychologic impact
• Cleansing
- Use mild soap, once or twice a day to control surface oiliness (frequent washing and abrasives can irritate the skin and increase sebum production and inflammation).
• Comedonal acne (grade 1): Keratinolytic agent preferred (1,3)[A]
• Mild inflammatory acne (grade 2): Topical antibiotic with benzoyl peroxide. Add keratinolytic agent if needed and tolerated (2,3)[A].
• Moderate inflammatory acne (grade 3): Systemic antibiotic added to regimen above for grade 2, or systemic antibiotic substituted for the topical treatment of benzoyl peroxide or topical antibiotic. Continue keratinolytic agent after completion of antibiotic for maintenance.
• Severe inflammatory acne (grade 4): As in Grade 3, or isotretinoin (1,3)[A]
• Apply topical agents to both lesions and surrounding area of affected skin.
• Topical retinoid plus antibiotic (topical or PO) is better than either alone (1,3)[A].
• Antibiotic therapy should be stopped after inflammatory lesions resolve.
• Oral antibiotics should generally be used for 6 months to prevent development of resistance. Topical antibiotic use should generally be limited to 3 months. Topical and oral antibiotics should not be used in combination.
• Recommended vehicle type
- Cream: Dry or sensitive skin, better in cold, dry weather
- Gel or solution: Oily skin, warmer, humid weather
- Lotion: Hair bearing areas
• Avoid use of drying agents in combination with keratinolytic agents.
• Oilfree, noncomedogenic sun screens
- Although UV light results in some improvement in untreated acne, it will react adversely with retinoids and tetracyclines.
• Stress management if acne flares with stress
Diet
• Good nutrition and hydration preferable
• Special diets do not diminish acne.
Activity
Cleansing after sweating
SPECIAL THERAPY
Phototherapy is effective for inflammatory lesions.
Complementary and Alternative Medicine
Zinc gluconate 30 mg/d may reduce inflammatory lesions (1)[B]
MEDICATION (DRUGS)
• Keratinolytic agents (1)[A]
- Side effects include dryness, erythema, scaling, and photosensitivity, which are dose related. Start with lower strength or frequency and increase as tolerated.
• Tretinoin (Retin-A, Retin A micro, Avita): Apply at bedtime; wash skin and let skin dry 30 minutes before topical application
- Retin-A Micro and Avita are less irritating, less phototoxicity.
- May cause an initial flare of lesions, which indicates a good initial response to treatment. May be eased by 14-day course of oral antibiotics
• Adapalene (Differin): Apply topically at night.
- As effective and better tolerated than tretinoin (1,2)[A]
• Tazarotene (Tazorac): Apply at bedtime.
- Highly effective
• Azelaic acid (Azelex): 20% topically, b.i.d.
- Keratinolytic, antibacterial, and antiinflammatory
- Reduces postinflammatory hyperpigmentation in dark-skinned individuals
- Side effects: Erythema, dryness, scaling, hypopigmentation
• Salicylic acid: Less effective than tretinoin
• Alpha-hydroxy acids: Available OTC
• Antibiotics and anti-inflammatories (1)[A]
- Daily to b.i.d. usage
• Topical benzoyl peroxide
- Bactericidal through direct toxic effect
- No P. acnes resistance noted
- Benzoyl peroxide 2.5% as effective as stronger preparations
- When used with tretinoin, apply benzoyl peroxide in morning and tretinoin at night
- Side effects: Irritation; may bleach clothes
• Topical antibiotics (1)[A]
- Erythromycin
- Clindamycin
- Metronidazole gel: Apply once daily
- Azelaic acid (Azelex): 20% cream: Enhanced bactericidal effect and decreased risk of resistant P. acnes when used with zinc and benzoyl peroxide
- Benzoyl peroxide-erythromycin (Benzamycin): Probably most effective topical antibiotic; especially effective with azelaic acid
- Benzoyl peroxide-clindamycin (BenzaClin, DUAC, Clindoxyl): Better than either alone (2)[A]
- Sodium sulfacetamide (Sulfacet-R, Novacet, Klaron): Useful in acne with seborrheic dermatitis or rosacea
• Systemic antibiotics (1)[A]
• Tetracycline: 500-2,000 mg/d, given b.i.d.-q.i.d.; begin at high dose, then taper in 4-6 months if good response; side effects include photosensitivity and esophagitis
- Avoid use with antacids, iron
• Minocycline 50-200 mg/d, q.i.d.-b.i.d.; side effects include photosensitivity, urticaria, gray-blue skin color, vertigo, autoimmune hepatitis, pseudotumor cerebri, and lupus-like syndrome
• Doxycycline 50-200 mg/d, given b.i.d.-q.i.d.; side effects include photosensitivity
• Erythromycin: 500-1,000 mg/d; given b.i.d.-q.i.d.; decreasing effectiveness as a result of increasing P. acnes resistance
• Trimethoprim-sulfamethoxazole (Bactrim DS)
• Isotretinoin (Accutane) (1)[A]: 0.5-1.0 mg/kg/d b.i.d. PO; 60-90% cure rate; usually given for 12-20 weeks, 20% of patients relapse and require retreatment.
- Side effects: Cheilitis, arthralgias, tendinitis, hyperlipidemia, pseudotumor cerebri, poor wound healing, highly teratogenic (severe central nervous system and cardiovascular anomalies and facial deformities)
- Avoid tetracyclines or vitamin A preparations during isotretinoin therapy
- Monitor for pregnancy, lipids and liver function tests at baseline, and every month.
- Should be registered member of manufacturer's iPLEDGE program
• Acne hyperpigmented macules
- Topical hydroquinones (1.5-10%)
- Azelaic acid (20%) topically
- Topical retinoids as above
• Other medications for women only
- Oral contraceptives (1)[A]: More improvement with 35 mcg estradiol than lower dose.
- Spironolactone (Aldactone); 25-200 mg/d; antiandrogen; reduces sebum production
- Flutamide (Eulexin) 250-500 mg/d
- Corticosteroids: Low dose, suppresses adrenal androgens. May be used in males with high-grade acne as well.
SURGERY
• Comedo extraction: Use a comedom extractor after incising the layer of epithelium over comedo
• Incision and drainage may be needed for abscesses
• Injection of large cystic lesions with 0.05-0.3 mL triamcinolone (Kenalog 2-5 mg/mL), use 30-gauge needle to inject and slightly distend cyst
• Acne scar treatment: Dermabrasion, chemical peels, laser resurfacing, grafting, subcutaneous incision, punch excision, punch elevation, tissue augmentation injections
FOLLOW-UP
DISPOSITION
Issues for Referral
Dermatology consultation recommended for the following: Refractory lesions despite appropriate therapy, consideration of isotretinoin therapy, management of acne scars
PROGNOSIS
Gradual improvement over time (usually within 8-12 weeks after beginning therapy)
COMPLICATIONS
• Acne conglobata: Severe confluent inflammatory acne with systemic symptoms
• Facial and psychological scarring
• Gram-negative folliculitis: Superinfection due to long-term oral antibiotic use, treatment with ampicillin, trimethoprim-sulfa, or isotretinoin
PATIENT MONITORING
• Monthly visits until adequate response
• Pretreatment and monthly lipids, liver function tests, and pregnancy tests when on isotretinoin
• Consider antibiotic resistance (60% overall) or gram-negative folliculitis if treatment fails
REFERENCES
1. Feldman S, Careccia RE, Barham KL, et al. Diagnosis and treatment of acne. Am Fam Physician. 2004;69(9):2123-2130.
2. Haider A, Shaw JC. Treatment of acne vulgaris. JAMA. 2004;292(6):726-735.
3. Webster G. Mechanism-based treatment of acne vulgaris: the value of combination therapy. J Drugs and Dermatol. 2005;4(3):281-288.

ACNE ROSACEA

2008-12-30T06:34:00.000-08:00

ACNE ROSACEA - LarryMillikan, MD
BASICS
DESCRIPTION
Chronic skin eruption with flushing and dilatation of small blood vessels in the face, especially nose and cheeks. Sometimes associated with ocular symptoms (ocular rosacea)
• System(s) Affected: Skin/Exocrine
• Synonym(s): Rosacea
ALERT
Geriatric Considerations
• Uncommon after age 60
• Unlikely in this age group
• Use of oral isotretinoin contraindicated
GENERAL PREVENTION
No preventive measure known
EPIDEMIOLOGY
• Predominant age: 30-50 years
• Predominant sex: Female > Male
Prevalence
Common
RISK FACTORS
Genetics
People of Northern European and Celtic background commonly afflicted
ETIOLOGY
• No proven cause
• Possibilities include
- Thyroid and gonadal disturbance
- Alcohol, coffee, tea, spiced food overindulgence (unproven)
- Demodex follicular parasite (suspected)
- Exposure to cold, heat, hot drinks
- Emotional stress
- Dysfunction of the gastrointestinal tract
- Environmental trigger factors: Sun, wind, cold
ASSOCIATED CONDITIONS
• Seborrheic dermatitis of scalp and eyelids
• Keratitis with photophobia, lacrimation, visual disturbance
• Corneal lesions
• Blepharitis
• Uveitis

DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Skin flush: Prominent at onset
• Redness: Lower half of nose, sometimes whole nose, forehead, cheeks, chin
Physical Exam
• Conjunctivae red: Sometimes
• Erythema, dusky: In advanced cases
• Blood vessels in involved area collapse under pressure
• Acne lesions form papules, pustules, and nodules
- Comedones are rare.
• Telangiectasia
• Rhinophyma: Sometimes (more common in males)
TESTS
Diagnosis based on physical exam findings
Pathological Findings
• Inflammation around hypertrophied sebaceous glands, producing papules, pustules, and cysts
• Absence of comedones and blocked ducts
• Vascular dilation and dermal lymphocytic infiltrate
DIFFERENTIAL DIAGNOSIS
• Drug eruptions (iodides and bromides)
• Granulomas of the skin
• Cutaneous lupus erythematosus
• Carcinoid syndrome
• Deep fungal infection
• Acne vulgaris
• Seborrheic dermatitis
• Steroid rosacea (abuse)
TREATMENT
GENERAL MEASURES
• Reassurance
• Treat psychological stress if present
• Avoid oil-based cosmetics
- Others are acceptable and may help women tolerate the symptoms.
• Electrodesiccation or chemical sclerosis of permanently dilated blood vessels
• Possible evolving laser therapy
Diet
No restrictions
Activity
• No restrictions
• Support physical fitness
MEDICATION (DRUGS)
First Line
• Low-dose oral tetracycline, 500-1,000 mg/d, or doxycycline, 50-150 mg/d, or minocycline, 75-200 mg/d; doxycycline, 20 mg PO b.i.d., 40 mg b.i.d. (oracea) if persistent
• Sulfur-containing local applications:
- Alcohol-sulfur (Liquimat)
- Sulfur (Fostril)
- Resorcinol-sulfur (Rezamid)
- Sulfacetamide-sulfur (Sulfacet-R, Nicosyn, Avar Gel, Avar Cleanser, Avar Green, Rosanil Cleanser, Plexion Cleanser, Ovace Wash, Clenia Emollient Cream, Clenia Foam Wash)
- Urea-sulfacetamide-sulfur (Rosula)
• Azelaic acid (Finacea) topically
• Topical metronidazole (MetroGel) 0.75% gel: 1% gel. Apply each morning and at bedtime after cleansing skin; also available as a cream and lotion, which may be better tolerated by some patients; or 1% cream formulation of metronidazole (Noritate), used once daily
• Topical erythromycin
• Topical clindamycin lotion preferred
• Possible utility of calcineurin inhibitors (tacrolimus, 0.1%; pimecrolimus, 0.1%)
• Topical steroids should not be used, as they may aggravate rosacea.
• Contraindications
- Tetracycline: Not for use during pregnancy or in children 8 years
- Isotretinoin: Teratogenic; not for use during pregnancy or in women of reproductive age who are not using reliable contraception
• Precautions: Tetracycline may cause photosensitivity; sunscreen recommended
• Significant possible interactions
- Tetracycline: Avoid concurrent administration with antacids, dairy products, or iron
- Broad-spectrum antibiotics: May reduce the effectiveness of oral contraceptives; barrier method recommended
Second Line
For severe cases, isotretinoin PO for 4 months
SURGERY
Surgical treatment of rhinophyma
FOLLOW-UP
DISPOSITION
Outpatient treatment
PROGNOSIS
• Slowly progressive
• Subsides spontaneously (sometimes)
COMPLICATIONS
• Rhinophyma (dilated follicles and thickened bulbous skin on nose), especially in men
• Conjunctivitis
• Blepharitis
• Keratitis
• Visual deterioration
PATIENT MONITORING
• Occasional and as needed
• Close follow-up for women using isotretinoin
REFERENCES
1. Fitzpatrick TB, et al., eds. Dermatology in General Medicine, 5th ed. New York: McGraw-Hill, 1999.
2. Habif T. Clinical Dermatology, 4th ed. St. Louis MO: Mosby, 2004.
3. Powell FC. Clinical practice. Rosacea. N Engl J Med. 2005;352:793-803.

ACETAMINOPHEN POISONING

2008-12-30T06:33:00.000-08:00

ACETAMINOPHEN POISONING - Lars C. Larsen, MD
BASICS
DESCRIPTION
• A disorder characterized by hepatic necrosis following large ingestions of acetaminophen. Symptoms may vary from initial nausea, vomiting, diaphoresis, and malaise to jaundice, confusion, somnolence, coma, and death. The clinical hallmark is the onset of symptoms within 24 hours of ingestion of acetaminophen-only or -combination products.
• Acetaminophen poisoning is most often encountered following large single ingestions of acetaminophen-containing medications. Usual toxic doses are >7.5 g in adults and 150 mg/kg in children. However, poisoning also occurs after acute and chronic ingestions of lesser amounts in susceptible individuals, including those who regularly abuse alcohol, are chronically malnourished, or take medications that affect hepatic metabolism of acetaminophen.
• Therapeutic adult doses are 0.5-1 q4-6h; up to a maximum of 4 g/d. Therapeutic pediatric doses are 10-15 mg/kg q4-6h, not to exceed 5 doses in 24 hours.
• System(s) Affected: Cardiovascular; Gastrointestinal; Renal/Urologic
• Synonym(s): Paracetamol poisoning
ALERT
Geriatric Considerations
Hepatic damage may be increased if taking hepatotoxic medications chronically.
Pediatric Considerations
Hepatic damage at toxic acetaminophen levels is decreased in children 6 years.
Pregnancy Considerations
• Increased incidence of spontaneous abortion, especially with overdose at early gestational age
• Incidence of spontaneous abortion or fetal death appears to be increased when N-acetylcysteine (NAC) treatment is delayed.
GENERAL PREVENTION
Parent/caregiver education essential:
• Education during well child exams regarding poisoning prevention
• Emergency telephone numbers
EPIDEMIOLOGY
• Predominant age: Children and adults at any age
• Predominant sex: No reported association
Incidence
• >131,700 ingestions of acetaminophen containing medications reported by poison control centers in 2004
• 327 deaths in 2004, 3 in children 6 years
Prevalence
Approximately 31% of exposures are in children 6 years.
RISK FACTORS
• Age 6 years
• Concurrent oral poisoning with other substances
• Psychiatric illness
• History of previous toxic ingestions or suicide attempts
• Regular ingestion of large amounts of alcohol
ETIOLOGY
Accidental or intentional ingestion of acetaminophen or combination medications containing acetaminophen

DIAGNOSIS
SIGNS AND SYMPTOMS
• Develop over the 1st 24 hours following large ingestions and may last as long as 8 days
• Severe symptoms indicate large ingestions or coingestants
• Fulminant hepatic failure occurs in 1% of adults and is very rare in children 6 years.
• Stage 1: 1st 24 hours
- Nausea
- Vomiting
- Diaphoresis
• Stage 2: 24-48 hours
- Right upper quadrant pain
- Typically less nausea, vomiting, diaphoresis, and malaise than in stage 1
• Stage 3: 72-96 hours
- Nausea, vomiting, malaise reappear
- Severe poisonings may result in jaundice, confusion, somnolence, and coma
• Stage 4: 7-8 days
- Resolution of clinical signs in survivors
• May develop gradually following long-term ingestion of near-therapeutic amounts of acetaminophen. Such patients may present in any stage 1-3, without a history of ingestion of the usual toxic doses.
TESTS
Lab
• Plasma acetaminophen levels should be drawn on all patients 4 hours or more after ingestion (levels prior to 4 hours not helpful).
• At least one additional acetaminophen level drawn 4-6 hours after the 1st level is recommended if the ingested acetaminophen is an extended-release product (e.g., Tylenol Extended Relief) or is not known to be an immediate-release product.
• If the second level is >1st level or is close to the "possible risk" level on the Rumack-Matthew nomogram, it may be prudent to obtain additional acetaminophen levels every 2 hours until the levels stabilize or decline.
• If coingestants include drugs that slow gastrointestinal motility, an acetaminophen level drawn 4-6 hours after the 2nd level may detect a late increase in serum acetaminophen concentration.
• Screens for suspected coingestants (aspirin, iron, and others) may be positive (especially when suicide is a possibility).
• With toxic ingestions, aspartate transaminase (AST; serum glutamic-oxaloacetic transaminase), alanine transaminase (serum glutamic-pyruvic transaminase), and bilirubin levels begin to rise in stage 2 and peak in stage 3. In severe poisonings, the prothrombin time will parallel these changes.
• AST levels >1,000 IU/L are consistent with the diagnosis, and levels of 20,000 IU/L are not uncommon.
• Laboratory abnormalities usually resolve by stage 4.
• Renal function abnormalities are common in patients with hepatotoxicity.
• Evidence of damage to the pancreas and heart may present following severe poisonings.
• Drugs that may alter lab results: None with clinically significant cross-reactivity with plasma acetaminophen assay
• Disorders that may alter lab results: Diseases or toxic substances that damage the liver, particularly alcohol
Imaging
No specific imaging required
Diagnostic Procedures/Surgery
None other than correlating plasma acetaminophen levels with the clinical presentation
Pathological Findings
Centrilobular hepatic necrosis
DIFFERENTIAL DIAGNOSIS
• Consider presence of coingestants, especially alcohol
• Other ingested toxins that produce severe acute hepatic injury, including the mushroom Amanita phalloides and products containing yellow phosphorus or carbon tetrachloride
TREATMENT
STABILIZATION
Contact a regional poison control center for management recommendations. In the United States, a local poison control center can be reached by calling (800) 222-1222.
GENERAL MEASURES
• Activated charcoal should be used (1,2)[C]; (3)[A], but preferably not within 1 hour of administration of the antidote NAC.
• The stomach of untreated patients may be emptied by gastric lavage if within 1 hour of ingestion.
• Ipecac is no longer recommended for routine use at home or in health care facilities (4)[C].
• NAC should be given (3)[A] when plasma acetaminophen concentrations measured 4 hours or more after ingestion are in the "possible risk" or higher levels on the Rumack-Matthew nomogram. This corresponds to acetaminophen levels >150 ug/mL (993 umol/L), >75 ug/mL (497 umol/L), and >40 ug/mL (265 umol/L) at 4, 8, and 12 hours after ingestion, respectively.
• NAC therapy may be effective up to 36 hours or more after ingestion
Diet
No special diet except with severe hepatic damage
Activity
Restricted if significant hepatic damage has occurred
MEDICATION (DRUGS)
First Line
• 2 classes of medicine
- Activated charcoal
- Acetylcysteine (NAC, Mucomyst)
• Emergency facility/hospital
- Patients evaluated within 1 hour of ingestion may have their stomachs evacuated by gastric lavage.
- Activated charcoal: 1 g/kg PO for initial dose; preferably not within 1 hour of NAC administration. Additional concurrent use during NAC therapy is controversial.
- Acetylcysteine PO or IV
 Oral loading dose of 140 mg/kg, followed by 70 mg/kg q4h for 17 additional doses. Whenever possible, NAC therapy should be initiated within 8 hours following the toxic ingestion.
 IV loading dose of Acetadote 150 mg/kg over 15 minutes X 1 (some recommend the loading dose be given over 60 minutes to decrease incidence of anaphylactoid rxns). Maintenance doses: 50 mg/kg over 4 hours, followed by 100 mg/kg over 16 hours.
• Contraindications: Medication allergies
• Precautions
- Oral NAC may cause significant nausea and vomiting due to its sulfur content; consider administration by nasogastric tube.
- Nausea can be treated with metoclopramide (Reglan), 0.5-1 mg/kg IV, or ondansetron (Zofran), 0.15 mg/kg IV (for age >4 years, usually 4 mg/dose).
- IV NAC (Acetadote) may cause anaphylactoid rxns including rash, bronchospasm, pruritis, angioedema, tachycardia, or hypotension.
• Reactions usually occur with loading dose. Slow or temporarily stop the infusion; may concurrently treat with antihistamines
• Significant possible interactions: Activated charcoal given within 1 hour of NAC may adsorb the NAC, thereby limiting its effectiveness.
Second Line
Oral racemethionine (methionine)
FOLLOW-UP
DISPOSITION
• All patients should be evaluated at a health care facility.
• Outpatient for nontoxic accidental ingestions
Admission Criteria
Toxic and intentional ingestions
Issues for Referral
Psychiatric follow-up after intentional ingestions
PROGNOSIS
• Complete recovery with early therapy
• 1% of adult patients develop hepatic failure.
• Hepatic failure is very rare in children 6 years.
COMPLICATIONS
Rare following recovery from acute poisoning
REFERENCES
1. Gaudreault P. Activated charcoal revisited. Clin Ped Emerg Med. 2005;6:76-80.
2. Heard K. Gastric Decontamination. Med Clin N Am. 2005;89:1067-1078.
3. Brok J, Buckley N, Glud C. Interventions for paracetamol (acetaminophen) overdoses. The Cochrane Database of Systematic Reviews. 2006; volume 1.
4. American Academy of Pediatrics Committee on Injury, Violence, and Poison Prevention. Poison treatment in the home. Pediatrics. 2003;112:1182-1185.
5. Acetylcysteine (Acetadote) for acetaminophen overdosage. The Medical Letter 2005;47:70-71.
6. Watson WA, Litovitz TL, Rodgers GC Jr, et al. 2004 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Amer J Emerg Med. 2005;23(pt 5)1: 589-666.